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YektaKooshali MH, SobhZahedi M, Razavi Tousi SMT, Hamidi M, Modiri L. Astaxanthin-loaded PLGA nanoparticles inhibit survival of MKN-45 gastric cancer cell line by modulating JAK2/STAT3/mTOR/PI3K pathway. BMC Cancer 2025; 25:44. [PMID: 39780129 PMCID: PMC11715247 DOI: 10.1186/s12885-024-13401-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 12/26/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/AIMS Gastric cancer (GC) is a significant global health issue with high incidence rates and poor prognoses, ranking among the top prevalent cancers worldwide. Due to undesirable side effects and drug resistance, there is a pressing need for the development of novel therapeutic strategies. Understanding the interconnectedness of the JAK2/STAT3/mTOR/PI3K pathway in tumorigenesis and the role of Astaxanthin (ASX), a red ketocarotenoid member of xanthophylls and potent antioxidant and anti-tumor activity, can be effective for cancer treatments. This study aimed to investigate the effect of ASX-loaded nanoparticles on the survival of MKN-45 GC cells and the expression of JAK2/STAT3/mTOR/PI3K, offering insights into potential targeted therapies for GC. METHODS The growth status and survival rate of MKN-45 GC cell lines were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT) assay, and the optimal IC50 concentration of ASX, PLGA, and ASX + PLGA was estimated. Also, the clonogenic assay was performed to determine the reproductive power and colony formation of under-treatment cells. Apoptosis and necroptosis of cells were evaluated using acridine orange (AO) staining. The western blot assessed the protein's level of expression and intensity (JAK2/STAT3/mTOR/PI3K). SPSS version 16 software was used for statistical analysis, P-value was considered lower than 0.05. RESULTS Based on the results, increasing concentrations of ASX and ASX + PLGA led to a decrease in the viability of MKN-45 cells compared to the control group (P < 0.001). This value was lower for cells treated with ASX + PLGA (P = 0.003). The IC50 values for each of the studied groups (ASX, ASX + PLGA, and PLGA) were 81.45 µg/ml, 51.45 µg/ml, and 3.383 mg/ml, respectively. The levels of expression and intensity of JAK2, STAT3, and mTOR proteins in the Western blotting analysis under ASX + PLGA treatment increased compared to the control group. Conversely, the levels of expression and intensity of P-JAK2, P-STAT3, and P-mTOR proteins in the ASX + PLGA treatment group decreased by 41%, 34%, 37%, and 43%, respectively, compared to the control group. Protein expression levels and intensities of JAK2, STAT3, and mTOR significantly increased when treated with PLGA, ASX, and ASX + PLGA compared to the control group (P < 0.001). CONCLUSIONS The encapsulation of ASX in PLGA nanoparticles enhances drug stability, enables targeted delivery, and allows for sustained release. This study highlights the therapeutic potential of ASX-loaded nanoparticles in targeting JAK2/STAT3/mTOR/PI3K pathways in GC treatment. Further research is needed to understand the mechanisms and clinical applications of this novel immunotherapy strategy.
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Affiliation(s)
- Mohammad Hossein YektaKooshali
- Medical Biotechnology Research Center, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Cellular and Molecular Biology, Lahijan Branch, Islamic Azad University, Lahijan, Iran
| | - Mahdieh SobhZahedi
- Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.
| | | | - Masoud Hamidi
- Université libre de Bruxelles (ULB), École polytechnique de Bruxelles - 3BIO-BioMatter, Avenue F.D. Roosevelt, 50 - CP 165/61, Brussels, 1050, Belgium
| | - Leila Modiri
- Department of Cellular and Molecular Biology, Lahijan Branch, Islamic Azad University, Lahijan, Iran.
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Zi M, Zhang Y, Hu C, Zhang S, Chen J, Yuan L, Cheng X. A literature review on the potential clinical implications of streptococci in gastric cancer. Front Microbiol 2022; 13:1010465. [PMID: 36386672 PMCID: PMC9643750 DOI: 10.3389/fmicb.2022.1010465] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 10/03/2022] [Indexed: 10/29/2023] Open
Abstract
Streptococcus is widely found in nature and the human body, and most species are not pathogenic. In recent years, studies have found that Streptococcus is associated with gastric cancer. Streptococcus was found to be enriched in the oral cavity, stomach and intestine of gastric cancer patients and found to be increased in gastric cancer tissues, suggesting that Streptococcus may be the pathogenic bacteria underlying gastric cancer. This review discusses the discovery of Streptococcus, the relationship between Streptococcus and gastric cancer, and the possible carcinogenic mechanism of Streptococcus and summarizes the progress of the research on the role of Streptococcus in gastric cancer to provide new ideas for the early detection, diagnosis and treatment of gastric cancer.
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Affiliation(s)
- Mengli Zi
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Yanqiang Zhang
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Can Hu
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Shengjie Zhang
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Jinxia Chen
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Li Yuan
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xiangdong Cheng
- Department of Gastric surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
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Lawi ZK, Al-Shuhaib MBS, Amara IB, Alkhammas AH. Two missense variants of the epidermal growth factor receptor gene are associated with non small cell lung carcinoma in the subjects from Iraq. Mol Biol Rep 2022; 49:11653-11661. [PMID: 36169894 DOI: 10.1007/s11033-022-07933-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/07/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Lung carcinoma is a foremost cause of cancer-related mortality worldwide. Variable genetic factors are associated with the development of lung cancer. This study was performed to evaluate the possible association of epidermal growth factor receptor (EGFR) gene polymorphisms with non small cell lung carcinoma (NSCLC) in Iraqi population. METHODS DNA samples were extracted from 100 patients and 100 controls. Four PCR fragments were designed to amplify four high-frequency variants within EGFR, namely rs1050171, rs2072454, rs2227984, and rs2227983. The PCR fragments were genotyped by single-strand conformation polymorphism (SSCP) method, and each genotype was subjected to direct sequencing. RESULTS Genotyping experiments confirmed the variability of three targeted variants, and logistic regression analysis showed that two of these variants (rs1050171 and rs2227983) tend to exhibit a significant association with NSCLC. Individuals with rs1050171:GA genotype showed a possible association with the increased risk of NSCLC (P = 0.0110; OD 5.2636; Cl95% 1.4630 to 18.9371). Individuals with rs2227983:GG genotype exhibited a potential association with NSCLC (P = 0.0037; OD 5.2683; Cl95% 1.7141 to 16.1919). Linkage disequilibrium analysis showed that the effects of the investigated variants seem to take independent actions, and no haplotype was found to be associated with the high prevalence of NSCLC. CONCLUSIONS Our collective data indicated that EGFR-rs1050171G/A and EGFR-rs2227983G/G SNPs tend to exert significant and separate associations with the increased risk of NSCLC. However, this study recommends using a broader spectrum of the investigated samples to get further details of both SNPs in terms of their association with the susceptibility to NSCLC.
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Affiliation(s)
- Zahraa K Lawi
- Department of Biology, College of Science, University of Kufa, Najaf, 54001, Iraq
| | - Mohammed Baqur S Al-Shuhaib
- Department of Animal Production, College of Agriculture, Al-Qasim Green University, Al-Qasim, Babil, 51001, Iraq.
| | - Ibtissem Ben Amara
- Laboratory of Medicinal and Environment Chemistry, Higher Institute of Biotechnology, University of SFAX, PB 261, 3000, Sfax, Tunisia
| | - Ahmed H Alkhammas
- Department of Animal Production, College of Agriculture, Al-Qasim Green University, Al-Qasim, Babil, 51001, Iraq
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Xiao P, Hua Z, Kang X, Lu B, Li M, Wu J, Dong W, Zhang J, Cheng C. Influence of Oral Intaking Habit on Tongue Coating Microbiota in Patients with Esophageal Precancerous Lesions. J Cancer 2022; 13:1168-1180. [PMID: 35281875 PMCID: PMC8899384 DOI: 10.7150/jca.67068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 12/25/2021] [Indexed: 11/05/2022] Open
Abstract
Background: Esophageal cancer (EC) is a common digestive tract tumor in China, and oral intaking habit has a great influence on the development of EC. The present study explored the correlation between oral intaking habit and tongue coating (TC) microbiota in patients with esophageal precancerous lesions (EPL) to provide a reasonable interpretation of the influence of oral intaking habit on microbial alterations in the EPL. Methods: A case-control study was designed with 123 EPL patients and 176 volunteers with mild esophagitis, and they were well matched using sex, age, and body mass index. The TC microbiota was profiled using high-throughput sequencing of the V3-V4 region of the 16S rRNA gene, and the serum levels of total bile acid (TBA) and interleukin-17α (IL-17α) were measured using enzyme-linked immunosorbent assay. Alpha diversity, community structure, and linear discriminant analysis were conducted, and Spearman correlation analysis was used to build the symbiotic network. Results: No significant differences were observed in the diversity and richness of the TC microbiota between the cases and controls (P > 0.05). TC Peptostreptococcus and Capnocytophaga were enriched in EPL patients. Stratified analysis showed that TC microbial composition was affected by both EPL and oral intaking habit; for example, Atopobium and Actinomyces were positively related to oral intaking habit scores in both the cases and controls, while Simonsiella was negatively correlated with oral intaking habit status in cases but positively correlated with oral intaking habit status in controls. Although serum TBA and IL-17α were not associated with EPL (P > 0.05), the daily-drinking cases had a higher level of serum TBA than the nondrinking cases (P < 0.05), and Helicobacter pylori (Hp) negative controls had a higher level of serum TBA than the Hp-positive controls (P < 0.05). The symbiotic networks were comprised of 71 significant correlations in the controls and 52 significant correlations in the cases. Conclusions: The development of EPL changed the TC microbiota and decreased the symbiotic complexity of the TC bacteria, which were also influenced by the cancer-related oral intaking habit. Bile acid may be a key factor mediating changes in TC microbiota.
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Affiliation(s)
- Pan Xiao
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Zhaolai Hua
- Yangzhong Cancer Institute, Yangzhong People's Hospital, Jiangsu Yangzhong 212200, China
| | - Xiaoyu Kang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Bin Lu
- Department of Oncology, Yangzhong People's Hospital, Yangzhong 212200, Jiangsu, China
| | - Meifeng Li
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Juan Wu
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Wei Dong
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Junfeng Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Chun Cheng
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
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Lin CT, Chen TH, Yang CC, Luo KH, Chen TH, Chuang HY. Epidermal Growth Factor Receptor (EGFR) Gene Polymorphism May be a Modifier for Cadmium Kidney Toxicity. Genes (Basel) 2021; 12:genes12101573. [PMID: 34680968 PMCID: PMC8535213 DOI: 10.3390/genes12101573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/25/2021] [Accepted: 10/01/2021] [Indexed: 11/16/2022] Open
Abstract
The results of many studies indicate that cadmium (Cd) exposure is harmful to humans, with the proximal tubule of the kidney being the main target of Cd accumulation and toxicity. Studies have also shown that Cd has the effect of activating the pathway of epidermal growth factor receptor (EGFR) signaling and cell growth. The EGFR is a family of transmembrane receptors, which are widely expressed in the human kidney. The aim of this study was to investigate the kidney function estimated glomerular filtration rate (eGFR), and its relationship with plasma Cd level and EGFR gene polymorphism. Using data from Academia Sinica Taiwan biobank, 489 subjects aged 30-70 years were analyzed. The demographic characteristics was determined from questionnaires, and biological sampling of urine and blood was determined from physical examination. Kidney function was assessed by the eGFR with CKD-EPI formula. Plasma Cd (ug/L) was measured by inductively coupled plasma mass spectrometry. A total of 97 single-nucleotide polymorphisms (SNPs) were identified in the EGFR on the Taiwan biobank chip, however 4 SNPs did not pass the quality control. Multiple regression analyses were performed to achieve the study aim. The mean (±SD) plasma Cd level of the study subjects was 0.02 (±0.008) ug/L. After adjusting for confounding variables, rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA types had higher eGFR (4.89 mL/min/1.73 m2 (p = 0.035), 5.54 mL/min/1.73 m2 (p = 0.03), 4.96 mL/min/1.73 m2 (p = 0.048) and 5.16 mL/min/1.73 m2 (p = 0.048), respectively). Plasma cadmium and rs845555 had an interactive effect on eGFR. In conclusion, EGFR polymorphisms could be modifiers of Cd kidney toxicity, in which rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA may be protective, and Cd interacting with rs845555 may affect kidney function.
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Affiliation(s)
- Chun-Ting Lin
- Department of Public, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-T.L.); (T.-H.C.)
| | - Ting-Hao Chen
- Department of Public, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-T.L.); (T.-H.C.)
| | - Chen-Cheng Yang
- Departments of Occupational Medicine and Family Medicine, Kaohsiung Municipal Siaogang Hospital, and Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Kuei-Hau Luo
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Tzu-Hua Chen
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, and Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Hung-Yi Chuang
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Public Health and Environmental Medicine, College of Medicine, and Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7312-1101 (ext. 6849)
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Deng W, Jin L, Zhuo H, Vasiliou V, Zhang Y. Alcohol consumption and risk of stomach cancer: A meta-analysis. Chem Biol Interact 2021; 336:109365. [PMID: 33412155 DOI: 10.1016/j.cbi.2021.109365] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 11/27/2020] [Accepted: 12/30/2020] [Indexed: 12/16/2022]
Abstract
Stomach cancer is one of the most common cancers in the world. The relationship between alcohol consumption and the risk of stomach cancer remains unclear. Epidemiology studies investigating this relationship have shown inconsistent findings. A meta-analysis was performed to explore the association between alcohol consumption and increased stomach cancer risk. Eighty-one epidemiology studies, including 68 case-control studies and 13 cohort studies, were included in this study. A significant association was found between alcohol consumption and increased risk of stomach cancer (OR = 1.20, 95% CI 1.12-1.27). To explore the source of the significant heterogeneity (p < 0.05, I2 = 86%), analysis was stratified by study type (case-control study and cohort study), control type (hospital-based control and population-based control), gender (male, female, and mix), race (White and Asian), region (United States, Sweden, China, Japan), subsite of stomach cancer, and type of alcohol. The stratified analyses found that region and cancer subsite are major sources of the high heterogeneity. The inconsistent results in different regions and different subsites might be related to smoking rates, Helicobacter pylori infection, obesity, and potential genetic susceptibility. The positive association between drinking and increased risk of stomach cancer is consistent in stratified analyses. The dose-response analysis showed a clear trend that a higher daily intake of alcohol is associated with a higher risk of stomach cancer.
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Affiliation(s)
- Wenting Deng
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
| | - Lan Jin
- Section of Surgical Outcomes and Epidemiology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Haoran Zhuo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
| | - Vasilis Vasiliou
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA; Yale Cancer Center, New Haven, CT, USA
| | - Yawei Zhang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Fecal Microbiome Alteration May Be a Potential Marker for Gastric Cancer. DISEASE MARKERS 2020; 2020:3461315. [PMID: 33014185 PMCID: PMC7519184 DOI: 10.1155/2020/3461315] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 08/08/2020] [Accepted: 08/31/2020] [Indexed: 12/13/2022]
Abstract
Although intestinal microbial dysbiosis was confirmed to be associated with many chronic diseases and health status through complicated interaction with the host, the effect on gastric cancer was less studied. In this study, we sequenced the 16S rRNA and 18S rRNA genes of fecal bacteria and fungi, respectively, in 134 gastric cancer patients and 58 healthy controls matched by age and gender. Propensity score matching (PSM) was adopted for adjusting diet habits and lifestyle, and 44 patients and 44 healthy controls (matching population) were enrolled. Serum antibody to H. pylori and metabolites of the matching population were detected. The positive rates of antibody to H. pylori between the patients and the control group did not reach the statistical difference. LEfSe analysis indicated that bacteria were more stable than fungi when adjusting diet and lifestyle. Veillonella, Megasphaera, and Prevotella 7 genus and Streptococcus salivarius subsp. Salivarius, Bifidobacterium dentium, and Lactobacillus salivarius species in bacteria were related to the risk of gastric cancer and showed a good diagnostic value in distinguishing the patients from healthy controls. Streptococcus mitis showed a risk effect for gastric cancer; however, the effect turned into be protective after PSM. Serum L-alanine, L-threonine, and methionol were positively associated with Veillonella and Streptococcus and several fungi genus. Overall, our findings indicated that fecal microbiome constitution alteration may be associated with gastric cancer through influencing the amino acid metabolism.
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Volkov AY, Safronova VM, Nered SN, Lyubchenko LN, Stilidi IS. GENETIC POLYMORPHISM OF RETROPERITONEAL MYXOID LIPOSARCOMA. ACTA ACUST UNITED AC 2020. [DOI: 10.21294/1814-4861-2020-19-3-89-96] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Objective: to detect new molecular genetic markers and therapeutic targets in retroperitoneal myxoid liposarcoma.Material and Methods. DNA samples isolated from tumor tissue and obtained from formalinfixed paraffin-embedded (FFPE) slides were used. DNA was extracted using the GeneRead DNA FFPE Kit (50) (Qiagen). High-throughput next generation sequencing (NGS) using the GeneReader Actionable Insights Tumor Panel (GRTP – 101X) on the QCI Analyzer version 1.1 platform (Qiagen) was used for molecular genetic analysis of 12 genes involved in carcinogenesis: KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, RAF1.Results. Targeted sequencing of retroperitoneal extra-organ myxoid liposarcoma demonstrated genetic heterogeneity. Our study was the first to describe mutations and polymorphic variants in genes, such as EGFR, PIK3CA, ALK, BRAF, ERBB2 / 3, ESR1, KIT, PDGFRA in myxoid liposarcoma.Conclusion. This study demonstrated a wide range of molecular genetic rearrangements in retroperitoneal extra-organ myxoid liposarcoma. Synonymous mutations in the EGFR (Q787Q) and PDGFRA (P567P) genes were detected in all cases (100 %). Missense mutations in the ERBB2 gene (P1170A) and synonymous mutations in the ALK (G845G) and BRAF genes were identified in 75 % of cases. Missense mutation in the PIK3CA gene (I391M) was detected in 25 % of cases. The gene polymorphisms presented in this paper are most likely involved in the carcinogenesis of retroperitoneal myxoid liposarcoma. Further studies with larger patient groups and multivariate analysis of long-term treatment results are required.
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Affiliation(s)
- A. Yu. Volkov
- N.N. Blokhin National Medical Research Centre of Oncology of the Health Ministry of Russia
| | - V. M. Safronova
- N.N. Blokhin National Medical Research Centre of Oncology of the Health Ministry of Russia
| | - S. N. Nered
- N.N. Blokhin National Medical Research Centre of Oncology of the Health Ministry of Russia
| | - L. N. Lyubchenko
- N.N. Blokhin National Medical Research Centre of Oncology of the Health Ministry of Russia;
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | - I. S. Stilidi
- N.N. Blokhin National Medical Research Centre of Oncology of the Health Ministry of Russia
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Associations of Interleukin-1 β with H. pylori-Induced Gastric Atrophy and Syndrome of Dampness-Heat in the Spleen and Stomach in Subjects with H. pylori-Related Gastric Diseases. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:6409485. [PMID: 32382299 PMCID: PMC7187723 DOI: 10.1155/2020/6409485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/10/2020] [Indexed: 01/10/2023]
Abstract
H. pylori-related gastric diseases (HPGD) are a series of gastric mucosal benign and malignant lesions associated with H. pylori infection. Exploring the pathogenesis of HPGD will be of great significance to prevent and treat gastric malignancy. Traditional Chinese medicine (TCM) syndrome is the essence of TCM, reflecting the state of whole body. Potential similarities of TCM syndrome may provide a new perspective in understanding development and treatment of diseases. To seek an early warning signal for gastric malignant pathology and similarities of TCM syndrome from the viewpoint of molecular biology, we examined the relationships among H. pylori, gastric pathology, and TCM syndrome and effects of Interleukin-1β (IL-1β) gene polymorphisms and expression on gastric pathology and TCM syndrome in HPGD. The results indicated that detection of H. pylori with differentiation of TCM syndrome may have a predictive function to gastric pathology. H. pylori may lead to gastric atrophy via enhancing IL-1β mRNA expression, and IL-1β mRNA overexpression in gastric mucosa may be one of the generality characteristics for H. pylori-negative subjects with syndrome of dampness-heat in the spleen and stomach.
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Rehman MYA, van Herwijnen M, Krauskopf J, Farooqi A, Kleinjans JCS, Malik RN, Briedé JJ. Transcriptome responses in blood reveal distinct biological pathways associated with arsenic exposure through drinking water in rural settings of Punjab, Pakistan. ENVIRONMENT INTERNATIONAL 2020; 135:105403. [PMID: 31864032 DOI: 10.1016/j.envint.2019.105403] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 10/28/2019] [Accepted: 12/09/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Groundwater Arsenic (As) contamination is a global public health concern responsible for various health implications and a neglected area of environmental health research in Pakistan. Because of interindividual differences in genetic predisposition, As-related health issues may not be equally distributed among the As-exposed population. However, till date, no studies have been conducted including multiple SNPs involved in As metabolism and disease risk using a linear mixed effect model approach to analyze peripheral blood transcriptomics results. OBJECTIVES In order to detect early responses on the gene expression level and to evaluate the impact of selected SNPs inferring disease risks associated with As exposure, we designed a systematic study to investigate blood transcriptomics profiles of 57 differentially exposed rural subjects living in drinking water As-contaminated settings of Lahore and Kasur districts in Punjab Province in southeast Pakistan. Exposure among the subjects was correlated with individual transcriptome responses applying urinary As profiles as the main biomarker for risk stratification. METHODS We performed whole genome gene expression analysis in blood of subjects using microarrays. Linear effect mixed models were applied for evaluating the combined impact of SNPs hypothetically increasing the risk for As exposure-induced health effects (GSTM1, GSTT1, As3MT, DNMT1, MTHFR, ERCC2 and EGFR). RESULTS Our findings confirmed important signaling, growth factor, cancer and other disease related pathways known to be associated with increased As exposure levels. In addition, upon implementing our integrative SNPs-based genetic risk factor, pathways associated with an increased risk of NAFLD and diabetes appeared significantly enhanced by down-regulation of genes NDUFV3, IKBKB, IL6R, ADIPOR1, PPARA, OGT and FOXO1. CONCLUSION We report the first comprehensive study applying state-of-the-art bioinformatics approaches to address multiple SNP-based inter-individual variability in adverse molecular responses among subjects exposed to drinking water As contamination in Pakistan thereby providing strong evidence of various gene expression targets associated with development of known As-related diseases.
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Affiliation(s)
- Muhammad Yasir Abdur Rehman
- Environmental Health Laboratory, Department of Environmental Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Marcel van Herwijnen
- Grow School of Oncology and Developmental Biology, Department of Toxicogenomics, Maastricht University, the Netherlands
| | - Julian Krauskopf
- Grow School of Oncology and Developmental Biology, Department of Toxicogenomics, Maastricht University, the Netherlands
| | - Abida Farooqi
- Environmental Hydro-Geochemistry Laboratory, Department of Environmental Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Jos C S Kleinjans
- Grow School of Oncology and Developmental Biology, Department of Toxicogenomics, Maastricht University, the Netherlands
| | - Riffat Naseem Malik
- Environmental Health Laboratory, Department of Environmental Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Jacco Jan Briedé
- Grow School of Oncology and Developmental Biology, Department of Toxicogenomics, Maastricht University, the Netherlands.
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Martins RS, Ahmed T, Farhat S, Shahid S, Fatima SS. Epidermal growth factor receptor rs17337023 polymorphism in hypertensive gestational diabetic women: A pilot study. World J Diabetes 2019; 10:396-402. [PMID: 31363386 PMCID: PMC6656705 DOI: 10.4239/wjd.v10.i7.396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/10/2019] [Accepted: 06/21/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Women with gestational diabetes mellitus have an increased risk of developing gestational hypertension, which can increase fetal and neonatal morbidity and mortality. In the past decade, single nucleotide polymorphisms in several genes have been identified as risk factors for development of gestational hypertension. The epidermal growth factor receptor activates tyrosine kinase mediated blood vessels contractility; and inflammatory cascades. Abnormalities in these mechanism are known to contribute towards hypertension. It is thus plausible that polymorphisms in the epidermal growth factor receptor gene would be associated with the development of hypertension in women with gestational diabetes.
AIM To determine whether the epidermal growth factor receptor rs17337023 SNP is associated with the occurrence of hypertension in gestational diabetic women.
METHODS This pilot case-control study was conducted at two tertiary care hospitals in Karachi, from January 2017-August 2018. Two hundred and two women at 28 week of gestation with gestational diabetes were recruited and classified into normotensive (n = 80) and hypertensive (n = 122) groups. Their blood samples were genotyped for epidermal growth factor receptor polymorphism rs17337023 using tetra-ARMS polymerase chain reaction. Descriptive analysis was applied on baseline data. Polymorphism data was analyzed for genotype and allele frequency determination using chi-squared statistics. In all cases, a P value of < 0.05 was considered significant.
RESULTS Subjects were age-matched and thus no difference was observed in relation to age of the study subjects (P >0.05). Body fat percentage was significantly higher in hypertensive females as compared to normotensive subjects (35.138 ± 4.29 Case vs 25.01 ± 8.28 Control; P < 0.05). Similarly, systolic and diastolic blood pressures among groups were significantly higher in hypertensive group than the normotensive group (P < 0.05). Overall epidermal growth factor receptor rs17337023 polymorphism genotype frequency was similar in both groups, with the heterozygous AT genotype (56 in Case vs 48 in Control; P = 0. 079) showing predominance in both groups. Furthermore, the odds ratio for A allele was 1.282 (P = 0.219) and for T allele was 0.780 (P = 0.221) in this study.
CONCLUSION This pilot study indicates that polymorphisms in rs17337023 may not be involved in the pathophysiology of gestational hypertension in gestational diabetes via inflammatory cascade mechanism. Further large-scale studies should explore polymorphism in epidermal growth factor receptor and other genes in this regard.
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Affiliation(s)
- Russell S Martins
- Medical College, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Taimur Ahmed
- Medical College, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Sabah Farhat
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Sana Shahid
- Department of Physiology, Sir Syed Medical College for Girls, Karachi, Pakistan
| | - Syeda Sadia Fatima
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Sindh 74800, Pakistan
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12
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Genetic Variants in EGFR/PLCE1 Pathway Are Associated with Prognosis of Esophageal Squamous Cell Carcinoma after Radical Resection. Curr Med Sci 2019; 39:385-390. [PMID: 31209807 DOI: 10.1007/s11596-019-2047-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 12/24/2018] [Indexed: 12/24/2022]
Abstract
Esophageal cancer (EC) is one of the most deadly malignant diseases. Several studies revealed that variations of the phospholipase C epsilon 1 (PLCE1) gene were associated with EC susceptibility. PLCE1 is located downstream of the epidermal growth factor receptor (EGFR) pathway. Presently, the single nucleotide polymorphisms (SNPs) of EGFR/PLCE1 genes and their associations with EC survival remain unclear. In this study, the associations between genetic variants in the EGFR/PLCE1 pathway and prognosis in 124 esophageal squamous cell carcinoma (ESCC) patients with radical resection were explored. The results showed that CC genotype of both PLCE1 rs17109671 and EGFR rs2072454 was associated with ESCC prognosis. Multivariate analysis revealed that patients with the two unfavorable genotypes had the worst overall survival (OS) or disease-free survival (DFS) (HR=6.099, 95%CI=1.903-19.552; HR=3.994, 95%CI=1.49-10.702, respectively). Additionally, combination of SNPs and tumor stage could better predict OS (for AUC, 0.774 vs. 0.709) and PFS (for AUC, 0.773 vs. 0.704) than tumor stage alone. In conclusion, genetic variants of the EGFR/PLCE1 may be predictors of the prognosis of ESCC after surgery. The individuals with the CC genotype of PLCE1 rs17109671 and EGFR rs2072454 should receive more aggressive treatments.
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Sun X, Xiang CJ, Wu J, Dong W, Zhan Z, Wang RP, Zhang JF. Relationship between serum inflammatory cytokines and lifestyle factors in gastric cancer. Mol Clin Oncol 2019; 10:401-414. [PMID: 30847182 DOI: 10.3892/mco.2019.1804] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 01/15/2019] [Indexed: 12/15/2022] Open
Abstract
Chronic inflammation is associated with increased risk of gastric cancer (GC), and GC risk is significantly associated with lifestyle. The aim of the present study was to explore the association between serum inflammatory cytokines and lifestyle factors in GC. A total of 20 serum inflammatory cytokines were measured in a hospital-based case-control population with 142 GC patients and 98 healthy controls. Controls without the selected healthy lifestyle factors were regarded as baseline, and correlation analysis was conducted to establish the association between serum inflammatory cytokines and lifestyle factors. The results demonstrated that several lifestyle factors (including eating fried and salty foods, eating quickly, smoking and drinking) could increase the risk of GC, while only eating fresh fruits could decrease the risk of GC. Correlation analysis revealed that increased serum interleukin (IL)-12/IL-23P40 levels was associated with GC risk as significant differences were observed in all lifestyle factors. Increased serum IL-8 was closely associated with smoking in GC patients, while increased IL-17α and IL-8 levels were associated with GC patients who ate salty foods. Increased IL-10 and decreased TGF-β levels were also associated with GC patients who ate fresh fruits. In conclusion, GC risk was strongly affected by lifestyle factors, which may regulate the expression of inflammatory cytokines and promote gastric carcinogenesis.
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Affiliation(s)
- Xian Sun
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Chun-Jie Xiang
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Juan Wu
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Wei Dong
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Zhen Zhan
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Rui-Ping Wang
- Department of Oncology, First Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.,Department of Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
| | - Jun-Feng Zhang
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
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14
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Bashir NA, Ragab ES, Khabour OF, Khassawneh BY, Alfaqih MA, Momani JA. The Association between Epidermal Growth Factor Receptor ( EGFR) Gene Polymorphisms and Lung Cancer Risk. Biomolecules 2018; 8:biom8030053. [PMID: 30011810 PMCID: PMC6164867 DOI: 10.3390/biom8030053] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 07/07/2018] [Accepted: 07/10/2018] [Indexed: 01/21/2023] Open
Abstract
Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk. A significant association was observed between the rs712829 SNP and lung cancer risk (p < 0.05) where the GG + GT genotypes were higher in lung cancer patients when compared to controls. In addition, no association was detected between rs712830, rs2072454, and rs11543848 SNPs and lung cancer risk. When patients were stratified according to the lung cancer type, a significant association was detected between both rs712829 and rs2072454 and adenocarcinoma lung cancer (p < 0.05). Haplotype analysis of all four SNPs showed a significant association between the TCCG haplotype and both lung cancer and the adenocarcinoma subtype (p < 0.001). In conclusion, EGFR rs712829, rs2072454 SNPs, and TCCG haplotypes are associated with a risk of lung cancer among Jordanians. Since genetic associations are affected by the genetic background of populations, more studies in other Arab populations are required to confirm the present findings.
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Affiliation(s)
- Nabil A Bashir
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Entesar S Ragab
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Omar F Khabour
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Basheer Y Khassawneh
- Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Jafar A Momani
- Respiratory Medicine Division, King Hussein Medical Center, Amman 11733, Jordan.
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15
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Gong L, Xia Y, Qian Z, Shi J, Luo J, Song G, Xu J, Ye Z. Overexpression of MYC binding protein promotes invasion and migration in gastric cancer. Oncol Lett 2018; 15:5243-5249. [PMID: 29552163 PMCID: PMC5840499 DOI: 10.3892/ol.2018.7944] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 12/08/2017] [Indexed: 12/28/2022] Open
Abstract
Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the β-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.
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Affiliation(s)
- Lijie Gong
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China
| | - Yingjie Xia
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
| | - Zhenyuan Qian
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
- Department of Gastrointestinal and Pancreatic Surgery, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
| | - Ji Shi
- Department of Breast and Thyroid Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310000, P.R. China
| | - Jungang Luo
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
| | - Guangyuan Song
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Ji Xu
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
- Department of Gastrointestinal and Pancreatic Surgery, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
| | - Zaiyuan Ye
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310000, P.R. China
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16
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A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients. Tumour Biol 2015; 37:7295-303. [PMID: 26666825 DOI: 10.1007/s13277-015-4543-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 11/27/2015] [Indexed: 02/06/2023] Open
Abstract
Genetic factors are known to affect the efficiency of therapy with monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer (mCRC). At present, the only accepted molecular marker predictive of the response to anti-EGFR mAbs is the somatic mutation of KRAS and NRAS as a marker of resistance to anti-EGFR. However, only a fraction of KRAS wild-type patients benefit from that treatment. In this study, we show that the EGFR gene polymorphism rs1050171 defines, independently of RAS mutational status, a sub-population of 11 % of patients with a better clinical outcome after anti-EGFR treatment. Median PFS for patients with the GG genotype was 10.17 months compared to 5.37 of those with AG + AA genotypes. Taken together, our findings could be used to better define CRC populations responding to anti-EGFR therapy. Further studies in larger independent cohorts are necessary to validate the present observation that a synonymous polymorphism in EGFR gene impacts on clinical responsiveness.
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17
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Ye P, Li Z, Jiang H, Liu T. SNPs in microRNA-binding sites in the ITGB1 and ITGB3 3'-UTR increase colorectal cancer risk. Cell Biochem Biophys 2015; 70:601-7. [PMID: 24777809 DOI: 10.1007/s12013-014-9962-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The purpose of the study was to investigate the potential associations between single-nucleotide polymorphisms (SNPs) in microRNA (miRNA)-binding sites in the integrin beta-1 (ITGB1) gene and integrin beta-3 (ITGB3) gene 3'-untranslated regions, and colorectal cancer (CRC) susceptibility in a Chinese population. A hospital-based case-control study was performed in 200 patients with CRC and 200 matched healthy donors. Two SNPs in miRNA binding of ITGB1 and ITGB3 genes (rs17468 and rs2317676) were genotyped by polymerase chain reaction-restrict fragment length polymorphism assay. The association between genotypes and CRC risk was evaluated by computing the odds ratio (OR) and 95 % confidence interval (CI) from multivariate unconditional logistic regression analyses. The frequency of the T genotype in ITGB1 rs17468 and G genotype in ITGB3 rs2317676 occurred more frequently in CRC patients than in controls (P < 0.05). We found that CT and TT genotypes of rs17468 were associated with a significantly increased risk of CRC (OR = 1.67, 95 % CI = 1.090-2.559 for CT + TT vs. CC), also the AG and GG genotype in ITGB3 rs2317676 (OR = 1.65, 95 % CI = 1.114-2.458 for AG + GG vs. AA). In conclusion, our results showed that both the ITGB1 rs17468 SNP and ITGB3 rs2317676 SNP were associated with an increased risk of CRC, which suggests that these 2 SNPs might contribute to CRC risk in a Chinese population.
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Affiliation(s)
- Pingjiang Ye
- Department of Colorectal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, 312000, Zhejiang, China
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18
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Tong GX, Liang H, Chai J, Cheng J, Feng R, Chen PL, Geng QQ, Shen XR, Wang DB. Association of risk of gastric cancer and consumption of tobacco, alcohol and tea in the Chinese population. Asian Pac J Cancer Prev 2015; 15:8765-74. [PMID: 25374204 DOI: 10.7314/apjcp.2014.15.20.8765] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
This study aimed at summarizing epidemiological research findings on associations between tobacco, alcohol and tea consumption and risk of gastric cancer (GC) in the Chinese population. The review searched PubMed, Embase, China National Knowledge Infrastructure (CNKI) and China Biology Medicine (CBM) databases and reference lists of review papers for all studies published in English or Chinese languages. Information extracted, via two independent researchers, from retrieved articles included first author, year of publication, study design, sample size, source of controls and adjusted odds ratio (OR) or relative risk (RR) with the corresponding 95% confidence intervals (CIs) for each category. Statistical analyses used software STATA version 12.0. The systematic search found 89 articles containing 25,821 GC cases and 135,298 non-cases. The overall random effects in terms of pooled OR and 95%CI for tobacco, alcohol and tea consumption were 1.62 (95%CI: 1.50-1.74), 1.57 (95%CI: 1.41-1.76) and 0.67 (95%CI: 0.59-0.76) respectively; while the heterogeneity among included studies ranged from 80.1% to 87.5%. The majority of subgroup analyses revealed consistent results with the overall analyses. All three behavioral factors showed statistically significant dose-dependent effects on GC (P<0.05). The study revealed that tobacco smoking and alcohol drinking were associated with over 1/2 added risk of GC, while tea drinking conferred about 1/3 lower risk of GC in the Chinese population. However, these results should be interpreted with caution given the fact that most of the included studies were based on a retrospective design and heterogeneity among studies was relatively high.
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Affiliation(s)
- Gui-Xian Tong
- Center for Health Management, School of Health Services Management, Anhui Medical University, Hefei, China E-mail :
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Satake M, Yamada Y, Atogami S, Yamaguchi K. The incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type 1 carriers in Japan. Leuk Lymphoma 2015; 56:1806-12. [DOI: 10.3109/10428194.2014.964700] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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20
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A Meta-Analysis on the Relations between EGFR R521K Polymorphism and Risk of Cancer. Int J Genomics 2014; 2014:312102. [PMID: 25401099 PMCID: PMC4221867 DOI: 10.1155/2014/312102] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2014] [Accepted: 09/09/2014] [Indexed: 12/11/2022] Open
Abstract
The EGFR R521K polymorphism has been shown to reduce the activity of EGFR; however, the association between EGFR R521K polymorphism and the risk of cancer remains inconclusive; therefore we performed a meta-analysis to evaluate the relationship between EGFR R521K polymorphism and susceptibility to cancer. Our results suggest that the EGFR R521K polymorphism is not associated with risk of cancer, but the different chemosensitivity to anticancer drugs may need further investigation.
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21
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Kim J, Cho YA, Choi WJ, Jeong SH. Gene-diet interactions in gastric cancer risk: A systematic review. World J Gastroenterol 2014; 20:9600-9610. [PMID: 25071358 PMCID: PMC4110595 DOI: 10.3748/wjg.v20.i28.9600] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 02/17/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk.
METHODS: A literature search was conducted in PubMed, EMBASE, and MEDLINE for articles published between January 2000 and July 2013, and 38 studies were identified. Previous studies included various dietary factors (e.g., fruits and vegetables, soybean products, salt, meat, and alcohol) and genetic variants that are involved in various metabolic pathways.
RESULTS: Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants. Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region. However, most previous studies have limitations, such as a small sample size and a retrospective case-control design. In addition, past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis.
CONCLUSION: Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.
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Yang PW, Hsieh MS, Huang YC, Hsieh CY, Chiang TH, Lee JM. Genetic variants of EGF and VEGF predict prognosis of patients with advanced esophageal squamous cell carcinoma. PLoS One 2014; 9:e100326. [PMID: 24945674 PMCID: PMC4063891 DOI: 10.1371/journal.pone.0100326] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Accepted: 05/22/2014] [Indexed: 12/15/2022] Open
Abstract
PURPOSE To investigate the association between genetic polymorphisms of growth factor-related genes and prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS A total of 334 ESCC patients with advanced tumor stages (stages IIB, III and IV) were enrolled in the study. The genotypes of 14 candidate single nucleotide polymorphisms (SNPs) involved in growth factor-related functions were analyzed using iPLEX Gold technology from the genomic DNA of peripheral leukocytes, and were correlated with the clinical outcome of patients. Serum levels of growth factors were examined by enzyme-linked immunosorbent assay (ELISA). RESULTS The genetic polymorphisms of EGF:rs4444903, EGF:rs2237051 and VEGF:rs2010963 showed significant associations with overall survival (OS) of advanced ESCC patients (A/A+ A/G vs. GG, [HR = 0.77, 95% CI = 0.60-0.99, P = 0.039 for rs4444903; A/G+ G/G vs. A/A, [HR = 0.74, 95% CI = 0.58-0.95, P = 0.019 for rs2237051; G/G+G/C vs. C/C, [HR] inves = 0.69, 95% CI = 0.50-0.95, P = 0.023 for rs2010963). EGFR:rs2227983 and 3 SNPs of PIK3CA also showed borderline significant correlation with OS of advanced ESCC patients (P = 0.058 for rs2227983; P = 0.069, 0.091 and 0.067 for rs6443624, rs7651265 and rs7621329 of PIK3CA respectively). According to cumulative effect analysis of multiple SNPs, patients carrying 4 unfavorable genotypes exhibited more than a 3-fold increased risk of mortality. Finally, both EGF and VEGF expression levels significantly associated with patient mortality. CONCLUSION The genetic variants and expression levels of EGF and VEGF can serve as prognostic predictors in patients with advanced ESCC, and thus provide more information for optimizing personalized therapies for patients with ESCC.
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Affiliation(s)
- Pei-Wen Yang
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Min-Shu Hsieh
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ya-Chuan Huang
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ching-Yueh Hsieh
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tzu-Hsuan Chiang
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jang-Ming Lee
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- * E-mail:
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Zhang J, Zhan Z, Wu J, Zhang C, Yang Y, Tong S, Wang R, Yang X, Dong W. Association among lifestyle, clinical examination, polymorphisms in CDH1 gene and Traditional Chinese Medicine syndrome differentiation of gastric cancer. J TRADIT CHIN MED 2014; 33:572-9. [PMID: 24660577 DOI: 10.1016/s0254-6272(14)60023-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To explore the association among life-style, clinical examination, polymorphisms in CDH1 gene and Traditional Chinese Medicine (TCM) syndrome differentiation of gastric cancer (GC). METHODS A hospital-based population of 387 GC patients was investigated in Jiangsu province. Relevant information regarding lifestyle and clinical examination were collected by a standard questionnaire. Four known single nucleotide polymorphisms (SNPs) in CDH1 were investigated by polymerase chain reaction-ligation detection reaction methods. Statistical analysis was conducted by SPSS 16.0 software. RESULTS The results showed that meal duration and the status of glutamic pyruvic transaminase were significantly associated with TCM syndrome differentiation of GC (both P < 0.05). None of the four SNPs in the E-cadherin (CDH1) gene achieved significant differences in their distributions among the nine syndrome types of GC (both P > 0.05). However, significant differences were observed in rs13689 genotype distributions between several pairs of syndrome types of GC, suggesting that rs13689 is correlated with the syndrome differentiation of GC. CONCLUSION Integrated analysis of lifestyle, clinical examination and CDH1 gene polymorphisms can contribute to a better understanding of the GC syndrome types and may improve the efficacy of interventions by stratifying disease according to TCM criteria.
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Hong L, Han Y, Brain L. The role of epidermal growth factor receptor in prognosis and treatment of gastric cancer. Expert Rev Gastroenterol Hepatol 2014; 8:111-7. [PMID: 24410474 DOI: 10.1586/17474124.2014.844648] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Despite tremendous efforts to reduce deaths due to gastric cancer, it represents the second leading cause of cancer-related deaths worldwide. EGF receptor (EGFR) plays important roles in gastric carcinogenesis by regulation of cell cycle, angiogenesis and apoptosis. This review evaluates the functions, mechanisms and clinical uses of EGFR in gastric cancer. Although EGFR targeted single therapy shows limited effect, the combination of EGFR targeted agents with traditional chemotherapy regimens may bring about important progress in cancer therapy. More clinical trials should be performed to clarify both the prognostic and therapeutic value of EGFR in gastric cancer.
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Affiliation(s)
- Liu Hong
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China
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Relationship between EGF, TGFA, and EGFR Gene Polymorphisms and Traditional Chinese Medicine ZHENG in Gastric Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:731071. [PMID: 24454509 PMCID: PMC3876898 DOI: 10.1155/2013/731071] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Revised: 10/23/2013] [Accepted: 11/20/2013] [Indexed: 02/06/2023]
Abstract
In traditional Chinese medicine (TCM), correct syndrome differentiation is the most important principle guiding the prescription of Chinese herbal formulae for the treatment of gastric cancer (GC). We aimed to reveal the genetic mechanisms underlying GC syndrome differentiation (ZHENG) in a population of 387 GC patients. Twenty-nine single nucleotide polymorphisms (SNPs) in EGF, TGFA, and EGFR were investigated. Two SNPs, rs11466285 in TGFA and rs884225 in EGFR, were significantly associated with the distribution of ZHENG (P < 0.05). The rs11466285 TT genotype increased the risk of damp heat with toxin (DHT) and deficiency of both Qi and yin (DQY) compared with obstruction of blood stasis (OBS). The rs884225 AA genotype could increase the risk of DQY and deficiency of both Qi and blood (DQB) compared with yin deficiency due to stomach heat (YDSH). Parallel comparison among the SNPs and syndrome types revealed that DQB was distinct from YDSH, disharmony between the liver and stomach, stagnation of phlegm muddiness (SPM), OBS, and other syndromes at several SNP loci (P < 0.05). The rs11466285 TT and rs884225 AA genotypes exhibit increased risk of DQB compared with OBS and SPM (P < 0.05), respectively. In conclusion, the formation of GC ZHENG was related to EGF, TGFA, and EGFR gene polymorphisms.
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