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Zhu H, Jiang W, Zhang Q, Yu C. The role of UPK1B in gastric cancer: multi-omics analysis and experimental validation. Discov Oncol 2025; 16:476. [PMID: 40189715 PMCID: PMC11973043 DOI: 10.1007/s12672-025-02263-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 03/28/2025] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND UPK1B has been implicated in various cancers; however, its mechanism of action in gastric cancer remains elusive. METHODS We utilized transcriptional data and clinical information, and mutation profiles from The Cancer Genome Atlas (TCGA) database to analyze UPK1B's expression and clinical relevance. Biological enrichment, immune microenvironment characterization, and drug sensitivity analyses were conducted. Functional assays, including proliferation, migration, invasion, and in vivo metastasis models, were used to validate UPK1B's role in gastric cancer. RESULTS UPK1B was significantly upregulated in gastric cancer and correlated with worse clinical outcomes, including advanced stages and reduced survival rates. Biological enrichment analysis revealed its involvement in cancer-related pathways such as DNA replication and immune regulation. UPK1B was negatively correlated with NK cells and M1 macrophages, indicating its role in immune evasion. Functional experiments demonstrated that knockdown of UPK1B significantly suppressed gastric cancer cell proliferation, invasion, and migration in vitro and reduced pulmonary metastases in vivo. Drug sensitivity analysis suggested that high UPK1B expression was associated with increased sensitivity to lapatinib and resistance to cisplatin. CONCLUSIONS UPK1B promotes tumor progression and modulates the immune microenvironment in gastric cancer, making it a potential therapeutic target for future research and clinical applications.
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Affiliation(s)
- Haixing Zhu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, People's Republic of China
| | - Wen Jiang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, People's Republic of China
| | - Qian Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, People's Republic of China
| | - Changjun Yu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, People's Republic of China.
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Okamoto H, Cap QH, Nomura T, Nabeshima K, Hashimoto J, Iyatomi H. Practical X-ray gastric cancer diagnostic support using refined stochastic data augmentation and hard boundary box training. Artif Intell Med 2025; 161:103075. [PMID: 39919469 DOI: 10.1016/j.artmed.2025.103075] [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: 10/02/2023] [Revised: 12/16/2024] [Accepted: 01/27/2025] [Indexed: 02/09/2025]
Abstract
Endoscopy is widely used to diagnose gastric cancer and has a high diagnostic performance, but it must be performed by a physician, which limits the number of people who can be diagnosed. In contrast, gastric X-rays can be taken by radiographers, thus allowing a much larger number of patients to undergo imaging. However, the diagnosis of X-ray images relies heavily on the expertise and experience of physicians, and few machine learning methods have been developed to assist in this process. We propose a novel and practical gastric cancer diagnostic support system for gastric X-ray images that will enable more people to be screened. The system is based on a general deep learning-based object detection model and incorporates two novel techniques: refined probabilistic stomach image augmentation (R-sGAIA) and hard boundary box training (HBBT). R-sGAIA enhances the probabilistic gastric fold region and provides more learning patterns for cancer detection models. HBBT is an efficient training method that improves model performance by allowing the use of unannotated negative (i.e., healthy control) samples, which are typically unusable in conventional detection models. The proposed system achieved a sensitivity (SE) for gastric cancer of 90.2%, higher than that of an expert (85.5%). Under these conditions, two out of five candidate boxes identified by the system were cancerous (precision = 42.5%), with an image processing speed of 0.51 s per image. The system also outperformed methods using the same object detection model and state-of-the-art data augmentation by showing a 5.9-point improvement in the F1 score. In summary, this system efficiently identifies areas for radiologists to examine within a practical time frame, thus significantly reducing their workload.
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Affiliation(s)
- Hideaki Okamoto
- Department of Applied Informatics, Graduate School of Science and Engineering, Hosei University, 3-7-2 Kajino, Koganei, 184-8584, Tokyo, Japan
| | - Quan Huu Cap
- Department of Applied Informatics, Graduate School of Science and Engineering, Hosei University, 3-7-2 Kajino, Koganei, 184-8584, Tokyo, Japan; AI Development Department, Aillis Inc., 2-2-1 Yaesu, Chuo, 104-0028, Tokyo, Japan
| | - Takakiyo Nomura
- Department of Radiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan
| | - Kazuhito Nabeshima
- Department of Radiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan
| | - Jun Hashimoto
- Department of Radiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan
| | - Hitoshi Iyatomi
- Department of Applied Informatics, Graduate School of Science and Engineering, Hosei University, 3-7-2 Kajino, Koganei, 184-8584, Tokyo, Japan.
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Khan N, Rehman B, Almanaa TN, Aljahdali SM, Waheed Y, Ullah A, Asfandayar M, Al-Harbi AI, Naz T, Arshad M, Sanami S, Ahmad S. A novel therapeutic approach to prevent Helicobacter pylori induced gastric cancer using networking biology, molecular docking, and simulation approaches. J Biomol Struct Dyn 2023; 42:13876-13889. [PMID: 37962871 DOI: 10.1080/07391102.2023.2279276] [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: 11/08/2022] [Accepted: 10/27/2023] [Indexed: 11/15/2023]
Abstract
Helicobacter pylori infects 50% of the world population and in 80% of cases, the infection progresses to the point where an ulcer develops leading to gastric cancer (GC). This study aimed to prevent GC by predicting Hub genes that are inducing GC. Furthermore, the study objective was to screen inhibitory molecules that block the function of predicted genes through several biophysical approaches. These proteins, such as Mucin 4 (MUC4) and Baculoviral IAP repeat containing 3 (BIRC3), had LogFC values of 2.28 and 3.39, respectively, and were found to be substantially expressed in those who had H. pylori infection. The MUC4 and BIRC3 inhibit apoptosis of infected cells and promote cancerous cell survival. The proteins were examined for their Physico-chemical characteristics, 3D structure and secondary structure analysis, solvent assessable surface area (SASA), active site identification, and network analysis. The MUC4 and BIRC3 expression was inhibited by docking eighty different compounds collected from the ZINC database. Fifty-seven compounds were successfully docked into the active site resulting in the lowest binding energy scores. The ZINC585267910 and ZINC585268691 compounds showed the lowest binding energy of -8.5 kcal/mol for MUC4 and -7.1 kcal/mol for BIRC3, respectively, and were considered best-docked solutions for molecular dynamics simulations. The mean root mean square deviation (RMSD) value for the ZINC585267910-MUC4 complex was 0.86 Å and the ZINC585268691-BIRC3 complex was 1.01 Å. The net MM/GBSA energy value of the ZINC585267910-MUC4 complex estimated was -46.84 kcal/mol and that of the ZINC585268691-BIRC3 complex was -44.84 kcal/mol. In a nutshell, the compounds might be investigated further as an inhibitor of the said proteins to stop the progress of GC induced by H. pylori.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Nadeem Khan
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
| | - Bushra Rehman
- Institute of Biotechnology and Microbiology, Bacha Khan University, Charsadaa, Pakistan
| | - Taghreed N Almanaa
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | | | - Yasir Waheed
- Office of Research, Innovation and Commercialization, Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, Pakistan
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon
| | - Asad Ullah
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
| | - Muhammad Asfandayar
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
| | - Alhanouf I Al-Harbi
- Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia
| | - Tahira Naz
- Department of Chemical and Life Sciences, Qurtuba University of Science and Technology, Peshawar, Pakistan
| | - Muhammad Arshad
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
| | - Samira Sanami
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Sajjad Ahmad
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
- Department of Computer Science, Virginia Tech, Blacksburg, VA, USA
- Department of Natural Sciences, Lebanese American University, Beirut, Lebanon
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Masood L, Müller A, Ali NZ, Mummadisetty A, Yahya A, Burugu SS, Sajid R, Lakkimsetti M, Sagireddy S, Abdin ZU, Nazir Z. A Narrative Literature Review on Sepsis: A Primary Manifestation of Colorectal Neoplasm. Cureus 2023; 15:e44803. [PMID: 37809261 PMCID: PMC10560076 DOI: 10.7759/cureus.44803] [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: 07/09/2023] [Accepted: 09/06/2023] [Indexed: 10/10/2023] Open
Abstract
Sepsis and colorectal cancer (CRC) exhibit a complex relationship that warrants further exploration. This review delves into the interplay of factors between sepsis and CRC, uncovering shared pathophysiological traits and potential bacterial associations. Understanding these connections could pave the way for earlier diagnosis, improved management, and enhanced outcomes in CRC patients. The role of immune system dysfunction, hypoalbuminemia, and specific microbial imbalances, such as Streptococcus bovis and Clostridium septicum, are discussed. Recognizing sepsis in CRC patients is crucial for timely intervention, and tailored approaches encompassing antibiotic therapy, source control measures, and cancer treatment are essential for comprehensive care. Monitoring biomarkers and ratios can provide valuable insights into complications and overall health outcomes. A multidisciplinary approach involving various specialists is necessary to address the global burden of CRC and its association with sepsis while exploring novel interventions, such as fecal microbiota transplantation and personalized care. We conducted a thorough search using reputable databases such as PubMed, Scopus, and Google Scholar to investigate the connection between sepsis and CRC. We refined our search terms, utilized sidebar filters, and examined references in selected articles. This meticulous process helped us create a comprehensive literature review and gain valuable insights into this relationship.
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Affiliation(s)
- Lalain Masood
- Department of Internal Medicine, Bahria University Health Sciences Campus, Karachi, PAK
| | - Agustina Müller
- Department of General Medicine, Austral University Hospital, Pilar, ARG
| | - Nayab Z Ali
- Department of Internal Medicine, Sialkot Medical College, Sialkot, PAK
| | - Anvitha Mummadisetty
- Department of Internal Medicine, Modern Government Maternity Hospital, Hyderabad, IND
| | - Anam Yahya
- Department of Pharmacology, Dr. D. Y. Patil Medical College, Navi Mumbai, IND
| | | | - Rabia Sajid
- Department of Internal Medicine, Mayo Hospital, Lahore, PAK
| | - Mohit Lakkimsetti
- Department of Internal Medicine, Mamata Medical College, Khammam, IND
| | - Sowmya Sagireddy
- Department of Internal Medicine, Coney Island Hospital, New York, USA
| | - Zain U Abdin
- Department of Internal Medicine, District Head Quarter Hospital, Faisalabad, PAK
| | - Zahra Nazir
- Department of Internal Medicine, Combined Military Hospital, Quetta, PAK
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Proton Pump Inhibitor Use and Risk of Gastric Cancer: Current Evidence from Epidemiological Studies and Critical Appraisal. Cancers (Basel) 2022; 14:cancers14133052. [PMID: 35804824 PMCID: PMC9264794 DOI: 10.3390/cancers14133052] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/16/2022] [Accepted: 06/19/2022] [Indexed: 12/12/2022] Open
Abstract
Proton pump inhibitors (PPIs) are used for maintaining or improving gastric problems. Evidence from observational studies indicates that PPI therapy is associated with an increased risk of gastric cancer. However, the evidence for PPIs increasing the risk of gastric cancer is still being debated. Therefore, we aimed to investigate whether long-term PPI use is associated with an increased risk of gastric cancer. We systematically searched the relevant literature in electronic databases, including PubMed, EMBASE, Scopus, and Web of Science. The search and collection of eligible studies was between 1 January 2000 and 1 July 2021. Two independent authors were responsible for the study selection process, and they considered only observational studies that compared the risk of gastric cancer with PPI treatment. We extracted relevant information from selected studies, and assessed the quality using the Newcastle−Ottawa scale (NOS). Finally, we calculated overall risk ratios (RRs) with 95% confidence intervals (CIs) of gastric cancer in the group receiving PPI therapy and the control group. Thirteen observational studies, comprising 10,557 gastric cancer participants, were included. Compared with patients who did not take PPIs, the pooled RR for developing gastric cancer in patients receiving PPIs was 1.80 (95% CI, 1.46−2.22, p < 0.001). The overall risk of gastric cancer also increased in patients with gastroesophageal reflux disease (GERD), H. pylori treatment, and various adjusted factors. The findings were also consistent across several sensitivity analyses. PPI use is associated with an increased risk of gastric cancer in patients compared with those with no PPI treatment. The findings of this updated study could be used in making clinical decisions between physicians and patients about the initiation and continuation of PPI therapy, especially in patients at high risk of gastric cancer. Additionally, large randomized controlled trials are needed to determine whether PPIs are associated with a higher risk of gastric cancer.
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Hereditary diffuse gastric cancer (HDGC). An overview. Clin Res Hepatol Gastroenterol 2022; 46:101820. [PMID: 34656755 DOI: 10.1016/j.clinre.2021.101820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/02/2021] [Accepted: 09/25/2021] [Indexed: 02/06/2023]
Abstract
It is estimated that up to 10% of gastric carcinomas show familial aggregation. In contrast, around 1-3 % (approximately 33,000 yearly) are genuinely hereditary. Hereditary diffuse gastric cancer (HDGC) is a rare malignancy characterized by autosomal dominant inheritance of pathological variants of the CDH1 and CTNNA1 genes encoding the adhesion molecules E-cadherin and α-catenin, respectively. The multifocal nature of the disease and the difficulty of visualizing precursor lesions by endoscopy underscore the need to be aware of this malignancy as surgical prevention can be fully protective. Here, we provide an overview of the main epidemiological, clinical, genetic, and pathological features of HDGC, as well as updated guidelines for its diagnosis, genetic testing, counseling, surveillance, and management. We conclude that HDGC is a rare, highly penetrant disease that is difficult to diagnose and manage, so it is necessary to correctly identify it to offer patients and their families' adequate management following the recommendations of the IGCL. A critical point is identifying a mutation in HDGC families to determine whether unaffected relatives are at risk for cancer.
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Zhang Y, Zhang PS, Rong ZY, Huang C. One stomach, two subtypes of carcinoma-the differences between distal and proximal gastric cancer. Gastroenterol Rep (Oxf) 2021; 9:489-504. [PMID: 34925847 PMCID: PMC8677565 DOI: 10.1093/gastro/goab050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/13/2021] [Accepted: 08/13/2021] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract, posing a significant risk to human health. Over the past 10 years, the pathological characteristics and the prognosis of GC have been determined based on the locations of the tumors that were then classified into two types-proximal and distal GC. This review focuses on the differences in epidemiology, etiology, cell source, pathological characteristics, gene expression, molecular markers, manifestations, treatment, prognosis, and prevention between proximal and distal GC to provide guidance and a basis for clinical diagnosis and treatment.
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Affiliation(s)
- Yuan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Peng-Shan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Ze-Yin Rong
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
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Xu C, Huang X, Huang Y, Liu X, Wu M, Wang J, Duan X. Naringin induces apoptosis of gastric carcinoma cells via blocking the PI3K/AKT pathway and activating pro‑death autophagy. Mol Med Rep 2021; 24:772. [PMID: 34490484 PMCID: PMC8441985 DOI: 10.3892/mmr.2021.12412] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 04/19/2021] [Indexed: 01/16/2023] Open
Abstract
Naringin (Nar) is one of the natural glycosides extracted from pomelo and other citrus fruits. It has various pharmacological activities, including anti‑inflammatory, antioxidant, anti‑proliferative and anti‑cancer. However, the underlying mechanisms by which Nar regulates apoptosis and autophagy in gastric cancer remain unclear. Thus, the present study aimed to assess the therapeutic effect of Nar and the underlying mechanisms. SNU‑1 cell proliferation was determined using Cell Counting Kit‑8 assay. Cell morphological changes were observed under a phase‑contrast microscope. The changes in the cell cycle were determined using flow cytometry analysis and the changes in cell apoptosis were determined using flow cytometry, Hoechst 33258 and TUNEL staining. The protein levels pertaining to the PI3K/AKT pathway and cell apoptosis and autophagy were monitored using western blot analysis. The results demonstrated that Nar significantly inhibited SNU‑1 cell growth and induced cell cycle arrest in the G0/G1 phase and cell apoptosis. Further mechanistic studies demonstrated that Nar blocked the PI3K/AKT pathway, activated cell autophagy and stimulated the expression of apoptosis‑associated protein cleaved caspase 3 and Bax, but decreased the expression of Bcl‑2. Preincubating SNU‑1 cells with 3‑methyladenine, a cell‑autophagy inhibitor, significantly alleviated the effects of Nar in promoting cell apoptosis and cleaved caspase 3 expression. It was concluded that Nar promoted SNU‑1 cell apoptosis via blocking the PI3K/AKT signaling pathway and activating cell autophagy.
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Affiliation(s)
- Cuixiang Xu
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
| | - Xiaoyan Huang
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
| | - Yubin Huang
- Clinical Department, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China
| | - Xiao Liu
- Clinical Department, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China
| | - Min Wu
- Department of Research, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
| | - Jianhua Wang
- Second Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
| | - Xianglong Duan
- Second Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
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Yamamoto M, Shimokawa M, Ohta M, Uehara H, Sugiyama M, Nakashima Y, Nakanoko T, Ikebe M, Shin Y, Shiokawa K, Morita M, Toh Y. Comparison of laparoscopic surgery with open standard surgery for advanced gastric carcinoma in a single institute: a propensity score matching analysis. Surg Endosc 2021; 36:3356-3364. [PMID: 34426875 DOI: 10.1007/s00464-021-08652-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 07/16/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Compared with open standard gastrectomy (OG), laparoscopic gastrectomy (LG) did not result in inferior disease-free survival for early-stage and locally advanced gastric cancer (AGC). However, whether LG for AGC in elderly patients is more beneficial than OG is unclear. METHODS This study examined 458 patients with AGC. The mortality, morbidity, and prognosis were compared by age, gender, T and N factors, and pathological stage in the LG and OG groups using propensity score matching analysis. For the final analysis, 151 pairs of patients were selected from at each group. RESULTS The results showed that no significant difference in mortality and morbidity existed between the two groups. The 5-year relapse-free survival (RFS) rates were 70% and 62% in the LG and OG groups, respectively (p = 0.104). The 5-year RFS rates in patients with pathological stages I, II, and III who had undergone LG were 84%, 80%, and 55%, respectively, and 78%, 70%, and 45%, respectively, in those who had undergone OG (p < 0.005). The 5-year RFS rates in nonelderly patients who underwent LG or OG were 75% and 68%, respectively, and 58% and 40%, respectively, in elderly patients who underwent LG or OG (p < 0.005). CONCLUSION The 5-year RFS rates in patients with AGC at each stage did not significantly differ between LG and OG. However, the benefits at 5-year RFS in patients who underwent LG compared with OG were larger in elderly patients than those in nonelderly patients.
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Affiliation(s)
- Manabu Yamamoto
- Department of Surgery, Fukuoka Sanno Hospital, 3-6-45 Momochi-hama, Sawara-ku, Fukuoka, 814-0001, Japan.
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
| | - Mototsugu Shimokawa
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Mitsuhiko Ohta
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Hideo Uehara
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Masahiko Sugiyama
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Yuichiro Nakashima
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Tomonori Nakanoko
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Masahiko Ikebe
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Yuki Shin
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Keiichi Shiokawa
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Masaru Morita
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Yasushi Toh
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
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Evaluation of dual time-point fluorodeoxyglucose PET/computed tomography imaging in gastric cancer. Nucl Med Commun 2021; 41:1322-1327. [PMID: 32956249 DOI: 10.1097/mnm.0000000000001290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND We aimed to evaluate the efficiency of dual time-point fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging in detecting primary and metastatic lesions in gastric cancer. METHODS Between May 2019 and January 2020, 52 patients with gastric carcinoma were prospectively involved in our study. And dual time-point FDG PET/CT imaging performed to the patients. Of detected primary and metastatic lesions, the ones that are better visualized or only appear in delayed imaging were visually identified. Also, maximum standardized uptake value (SUVmax) of the primary and metastatic lesions and the intact liver tissue were measured in early and delayed imaging. Acquired SUVmax values and SUVmax ratios were compared statistically. RESULTS In delayed images, lesions were better visualized in 32 patients (61.5%) and extra lesions were detected in 4 patients (7.7%). SUVmax of primary tumor, SUVmax of liver metastases, SUVmax of lymph node metastases, primary tumor SUVmax/liver SUVmax ratio and lymph node metastasis SUVmax/liver SUVmax ratio were significantly higher in delayed images (P < 0.001, P = 0.022, P < 0.001, P < 0.001, P < 0.001, respectively). However, SUVmax of liver parenchyma was significantly lower in delayed images (P < 0.001). CONCLUSIONS There is a visually and statistically significant increase in the number and detectability of lesions seen in delayed images and dual time-point FDG PET/CT imaging seems useful in detecting primary and metastatic lesions in gastric cancer.
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11
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Trivanovic D, Plestina S, Honovic L, Dobrila-Dintinjana R, Vlasic Tanaskovic J, Vrbanec D. Gastric cancer detection using the serum pepsinogen test method. TUMORI JOURNAL 2021; 108:386-391. [PMID: 33993805 DOI: 10.1177/03008916211014961] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Gastric cancer (GC) is the eighth most common cause of cancer deaths in Croatia and one of the most common causes of cancer deaths worldwide. A reliable diagnostic tool for the early detection of GC is essential. OBJECTIVE We previously suggested a pepsinogen test method to reduce the mortality from GC by allowing early detection. Here, we report an updated analysis from a prospective single-center clinical study to evaluate the sensitivity and specificity of the pepsinogen test method and to determine whether this test can be used as a part of routine laboratory assessment of high-risk patients. METHODS We present mature data of the pepsinogen test method in the Croatian population after a median follow-up of 36 months. Statistical analyses were performed using a Mann-Whitney U test, multiple logistic regression, and receiver operating characteristics (ROC) to evaluate the predictive power of the assayed biomarkers. RESULTS Of the 116 patients, 25 patients had GC and 91 demonstrated a nonmalignant pathology based on tissue biopsy. Cutoff values were pepsinogen I ⩽70 and pepsinogen I/II ratio ⩽3.0. Using ROC curve analysis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were determined to be 87.22%, 78.12%, 90.10%, 71.43%, and 92.86%, respectively, for the diagnosis of GC. The area under the curve was 0.700 (95% confidence interval 0.57-0.83). CONCLUSION Pepsinogen tests are valuable for screening a population in need of further diagnosis and could help to avoid unnecessary invasive endoscopic procedures.
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Affiliation(s)
- Dragan Trivanovic
- Department of Oncology and Medical Faculty, General Hospital Pula, Pula, Croatia
| | - Stjepko Plestina
- Department of Oncology and Radiotherapy, Clinical Hospital Zagreb, Zagreb, Croatia
| | - Lorena Honovic
- Department of Clinical Chemistry and Medical Faculty, General Hospital Pula, Pula, Croatia
| | | | | | - Damir Vrbanec
- Department of Oncology and Medical Faculty, General Hospital Pula, Pula, Croatia
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Yang K, Lu L, Liu H, Wang X, Gao Y, Yang L, Li Y, Su M, Jin M, Khan S. A comprehensive update on early gastric cancer: defining terms, etiology, and alarming risk factors. Expert Rev Gastroenterol Hepatol 2021; 15:255-273. [PMID: 33121300 DOI: 10.1080/17474124.2021.1845140] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Early gastric cancer (EGC) is a well-defined gastric malignancy that is limited to the mucosa or submucosa, irrespective of lymph node metastasis. At an early stage, gastric cancer often does not cause symptoms until it becomes advanced, and it is a heterogeneous disease and usually encountered in its late stages. AREA COVERED This comprehensive review will provide a novel insight into the evaluation of EGC epidemiology, defining terms, extensive etiology and risk factors, and timely diagnosis since prevention is an essential approach for controlling this cancer and reducing its morbidity and mortality. EXPERT OPINION The causative manner of EGC is complex and multifactorial. In recent years, researchers have made significant contributions to understanding the etiology and pathogenesis of EGC, and standardization in the evaluation of disease activity. Though the incidence of this cancer is steadily declining in some advanced societies owing to appropriate interventions, there remains a serious threat to health in developing nations. Early detection of resectable gastric cancer is crucial for better patient outcomes.
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Affiliation(s)
- Kuo Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Lijie Lu
- Department of Digestive Diseases, Dongfang Hospital of Beijing University of Chinese Medicine , Beijing, PR, China
| | - Huayi Liu
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Xiujuan Wang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Ying Gao
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Liu Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Yupeng Li
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Meiling Su
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Ming Jin
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital , Tianjin, PR, China
| | - Samiullah Khan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital , Tianjin, PR, China
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13
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Intestinal bacteria are potential biomarkers and therapeutic targets for gastric cancer. Microb Pathog 2021; 151:104747. [PMID: 33484807 DOI: 10.1016/j.micpath.2021.104747] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 01/12/2021] [Accepted: 01/13/2021] [Indexed: 12/13/2022]
Abstract
The diagnostic and therapeutic role of intestinal microbiota in gastric carcinogenesis remains unclear. In this study, feces from gastric cancer patients and healthy people were sequenced for microbiota analysis, and the correlation between fecal bacteria and the occurrence of gastric cancer was explored. The β-diversity results showed that microbial compositions varied between gastric cancer patients and healthy people. Interestingly, the dissection of microbial structure revealed that all facultative anaerobic genera with relatively high abundances expanded significantly in gastric cancer patients. The succeeding correlation analysis demonstrated a distorted interaction of intestinal bacteria in gastric cancer. The application of some differential bacteria, Desulfovibrio, Escherichia, Faecalibacterium or Oscillospira, as biomarkers to predict gastric cancer could all reach an accuracy of 0.900 or above. The shift in Desulfovibrio was specifically verified by qPCR in newly collected fecal samples, and the patients with stage IV gastric cancer were identified to have significantly more Desulfovibrio than those with stage I, II and III gastric cancer. The possible role of Desulfovibrio in gastric cancer was assessed with H2S-treated HT-29 cells, and the results showed that H2S induced NO, IL-1β and IL-18 production, which is important for inflammation promotion and can be delivered through the bloodstream. This study suggests a correlation of intestinal microbiota and the development of gastric cancer.
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Zhu H, Chen Y, Zhang J, Qian C, Qiu W, Shen H, Shen Z. Knockdown of TRIM37 Promotes Apoptosis and Suppresses Tumor Growth in Gastric Cancer by Inactivation of the ERK1/2 Pathway. Onco Targets Ther 2020; 13:5479-5491. [PMID: 32606764 PMCID: PMC7297455 DOI: 10.2147/ott.s233906] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 05/20/2020] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE Gastric cancer (GC), a malignant tumor of the gastric mucosa, is the second leading cause of cancer deaths worldwide. Although the incidence and mortality of gastric cancer have been reduced in the US and elsewhere, it is still a major public health concern. In this study, we attempted to investigate the function of tripartite motif-containing protein 37 (TRIM37) in GC cell lines in order to propose a new therapy for GC. METHODS The expression of TRIM37 in GC patients and cell lines was detected by immunohistochemistry, real-time PCR and Western blotting analysis. After TRIM37 knockdown or overexpression, the cell cycle, proliferation and apoptosis, as well as the expression of related proteins, were detected. In addition, in vivo experiments on nude mice were performed. RESULTS We found that TRIM37 expression was significantly elevated in tumor tissues of GC patients and GC cell lines, and patients with high expression of TRIM37 had a poor prognosis. Knockdown of TRIM37 in GC cells significantly inhibited cell proliferation and cell cycle progression, promoted apoptosis, increased cleaved caspase 3 and decreased c-myc and phosphorylation of protein kinase 1/2 (p-ERK1/2). Effects of TRIM37 overexpression were opposite to that of TRIM37 knockdown and were potently attenuated by an ERK1/2 inhibitor. In addition, an ERK1/2 agonist increased TRIM37 and p-ERK1/2 in a dose-dependent manner, and TRIM37 knockdown potently attenuated EGF-induced cell proliferation and expression of TRIM37 and p-ERK1/2. Interestingly, we found that TRIM37 overexpression did not affect the mRNA level of dual-specificity phosphatase 6 (DUSP6), but reduced its protein level in GC cells. Co-immunoprecipitation (Co-IP) analyses revealed that TRIM37 interacted with DUSP6, and TRIM37 overexpression enhanced DUSP6 ubiquitination in GC cells. In vivo experiments on nude mice showed the inhibitory effect of TRIM37 knockdown on tumor growth. CONCLUSION These findings suggest that TRIM37 may act as an oncogene in the growth of GC cells and illustrate its potential function as a target in the treatment of GC.
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Affiliation(s)
- Hongyi Zhu
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
| | - Yuanwen Chen
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
| | - Jie Zhang
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
| | - Changlin Qian
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
| | - Weiqing Qiu
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
| | - Huojian Shen
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
| | - Zhiyong Shen
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai201112, People’s Republic of China
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Dias AR, Pereira MA, Ramos MFKP, Oliveira RJ, Ribeiro U, Zilberstein B, Cecconello I. Prediction scores for complication and recurrence after multivisceral resection in gastric cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1097-1102. [PMID: 31987704 DOI: 10.1016/j.ejso.2020.01.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 10/29/2019] [Accepted: 01/07/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Multivisceral resection (MVR) is indicated in T4b gastric cancer (GC) when R0 can be achieved. Patient's selection for MVR is imperative, since it carries an increased risk for postoperative complications (POC) and disease recurrence. This study aims to elaborate prediction scores for POC and recurrence after MVR for cT4b GC. METHODS Patients who underwent MVR with curative intent due to cT4b gastric adenocarcinoma were selected from our prospective database. Scoring models were based on the variables identified as risk factors for the studied outcome. Through binary regression the model that best predicted the outcome was created. RESULTS From 237 MVRs, 58 fulfilled the inclusion criteria. Males were 70.7%, mean age was 61.8 years. A pT4b was confirmed in 34 patients, 29 had 2 or more adjacent organs removed. Major POC occurred in 25.9%, mortality was 8.6%. Overall survival (OS) and disease-free survival (DFS) were similar for pT4b and non-pT4b. DFS was worse for pN+ and when >2 adjacent organs were removed. Scoring models included 5 and 6 parameters for POC and recurrence, respectively, and their accuracy was 80.6% (95%CI = 0.69-0.92) and 78% (95%CI = 0.66-0.90). The POC and recurrence rates in low- and high-score groups were statistically different (p < 0.001 and p = 0.004, respectively). Patients with high-risk for POC had lower OS (p = 0.036) and DFS was worse in the high-recurrence risk group (p = 0.008). CONCLUSION The proposed scoring systems accurately predict POC and recurrence in GC patients undergoing MVR. These models are easy to use and can assist in the adoption of an individualized approach.
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Affiliation(s)
- Andre Roncon Dias
- Cancer institute, Hospital das Clinicas, University of São Paulo School of Medicine, Sao Paulo, Brazil.
| | - Marina Alessandra Pereira
- Cancer institute, Hospital das Clinicas, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | | | - Rodrigo Jose Oliveira
- Cancer institute, Hospital das Clinicas, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Ulysses Ribeiro
- Cancer institute, Hospital das Clinicas, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Bruno Zilberstein
- Cancer institute, Hospital das Clinicas, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Ivan Cecconello
- Cancer institute, Hospital das Clinicas, University of São Paulo School of Medicine, Sao Paulo, Brazil
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Renzulli M, Clemente A, Spinelli D, Ierardi AM, Marasco G, Farina D, Brocchi S, Ravaioli M, Pettinari I, Cescon M, Reginelli A, Cappabianca S, Carrafiello G, Golfieri R. Gastric Cancer Staging: Is It Time for Magnetic Resonance Imaging? Cancers (Basel) 2020; 12:1402. [PMID: 32485933 PMCID: PMC7352169 DOI: 10.3390/cancers12061402] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 05/17/2020] [Accepted: 05/28/2020] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is a common cancer worldwide. Its incidence and mortality vary depending on geographic area, with the highest rates in Asian countries, particularly in China, Japan, and South Korea. Accurate imaging staging has become crucial for the application of various treatment strategies, especially for curative treatments in early stages. Unfortunately, most GCs are still diagnosed at an advanced stage, with the peritoneum (61-80%), distant lymph nodes (44-50%), and liver (26-38%) as the most common metastatic locations. Metastatic disease is limited to the peritoneum in 58% of cases; in nonperitoneal distant metastases, the most involved GC metastasization site is the liver (82%). The eighth edition of the tumor-node-metastasis staging system is the most commonly used system for determining GC prognosis. Endoscopic ultrasonography, computed tomography, and 18-fluorideoxyglucose positron emission tomography are historically the most accurate imaging techniques for GC staging. However, studies have recently shown renewed interest in magnetic resonance imaging (MRI) as a useful tool in GC staging, especially for distant metastasis assessment. The technical improvement of diffusion-weighted imaging and the increasing use of hepatobiliary contrast agents have been shown to increase the diagnostic performance of MRI, particularly for detecting peritoneal and liver metastasis. However, no principal oncological guidelines have included the use of MRI as a first-line technique for distant metastasis evaluation during the GC staging process, such as the National Comprehensive Cancer Network Guidelines. This review analyzed the role of the principal imaging techniques in GC diagnosis and staging, focusing on the potential role of MRI, especially for assessing peritoneal and liver metastases.
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Affiliation(s)
- Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Alfredo Clemente
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (A.R.); (S.C.)
| | - Daniele Spinelli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology, ASST Santi Paolo e Carlo, San Paolo Hospital, 20142 Milan, Italy; (A.M.I.); (G.C.)
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
| | - Davide Farina
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, 25138 Brescia, Italy;
| | - Stefano Brocchi
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Matteo Ravaioli
- General and Transplant Surgery Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (M.R.); (M.C.)
| | - Irene Pettinari
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Matteo Cescon
- General and Transplant Surgery Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (M.R.); (M.C.)
| | - Alfonso Reginelli
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (A.R.); (S.C.)
| | - Salvatore Cappabianca
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (A.R.); (S.C.)
| | - Gianpaolo Carrafiello
- Diagnostic and Interventional Radiology, ASST Santi Paolo e Carlo, San Paolo Hospital, 20142 Milan, Italy; (A.M.I.); (G.C.)
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
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Oh HJ, Yoon BH, Ha YC, Suh DC, Lee SM, Koo KH, Lee YK. The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis. Osteoporos Int 2020; 31:267-275. [PMID: 31776636 DOI: 10.1007/s00198-019-05220-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 11/01/2019] [Indexed: 12/24/2022]
Abstract
UNLABELLED Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.
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Affiliation(s)
- H J Oh
- Division of Gastroenterology, Department of Internal Medicine, Center for Cancer Prevention and Detection, National Cancer Center, Goyang-si, Republic of Korea
| | - B-H Yoon
- Department of Orthopaedic Surgery, Inje University College of Medicine, Seoul Paik Hospital, Seoul, Republic of Korea
| | - Y-C Ha
- Department of Orthopaedic Surgery, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - D-C Suh
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - S-M Lee
- College of Pharmacy, Daegu Catholic University , 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si,Gyeongbuk, 38430, Republic of Korea.
| | - K-H Koo
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, 463-707, Republic of Korea
- Department of Orthopedic Surgery, Seoul National University College of Medicine, 166 Gumi-ro, Bundang-gu, Seongnam-si, 463-707, Republic of Korea
| | - Y-K Lee
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, 463-707, Republic of Korea.
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18
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Liu X, Long Z, Cai H, Yu S, Wu J. TRIM58 suppresses the tumor growth in gastric cancer by inactivation of β-catenin signaling via ubiquitination. Cancer Biol Ther 2019; 21:203-212. [PMID: 31747856 PMCID: PMC7012179 DOI: 10.1080/15384047.2019.1679554] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 09/26/2019] [Accepted: 10/06/2019] [Indexed: 12/16/2022] Open
Abstract
Objective: To investigate and define the underlying molecular mechanism of tripartite motif-containing 58 (TRIM58) in regulating the tumor growth of gastric cancer (GC).Methods: TRIM58 expression in GC tissues and cells was detected by real-time PCR and Western blot, followed by lentiviral-induced overexpression or knockdown of TRIM58. Subsequently, CCK8, BrdU-ELISA, flow cytometry, immunoprecipitation, in vitro animal experiments and immunochemistry were performed to explore the function of TRIM58. Western blotting was used to detect β-catenin, C-myc, Cyclin D1, and survivin expression.Results: TRIM58 expression was significantly reduced in tumor tissues of GC patients and GC cell lines, whereas β-catenin, C-myc, Cyclin D1, and survivin were highly expressed. Overexpression of TRIM58 in GC cells resulted in decreases in β-catenin, C-myc, Cyclin D1, and survivin protein expression and significantly suppressed proliferation by preventing cell-cycle progression and promoting cell apoptosis. Conversely, TRIM58 knockdown resulted in the opposite effects. Furthermore, the effect of TRIM58 knockdown on GC cells was potently reversed by a β-catenin inhibitor, XAV939. Immunoprecipitations showed the interaction between TRIM58 and β-catenin, and TRIM58 overexpression significantly enhanced β-catenin degradation. In addition, we found a significant decrease in the growth and weight of tumors and an increase in tumor cell apoptosis in TRIM58-overexpression nude mice, which were also accompanied by reduced β-catenin expression.Conclusions: These data suggest that TRIM58 may function as a tumor suppressor in GC and potentially suppress the tumor growth of gastric cancer by inactivation of β-catenin signaling via ubiquitination.
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Affiliation(s)
- Xiaowen Liu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ziwen Long
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hong Cai
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shengjia Yu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianghong Wu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Saw KS, Robertson J, Walsh M, Hider P, Rodgers M, Booth M, Srinivasa S, Koea J. Treatment of gastric adenocarcinoma at a New Zealand centre: meeting the challenges of a low volume country. ANZ J Surg 2019; 90:81-85. [DOI: 10.1111/ans.15543] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/27/2019] [Accepted: 10/05/2019] [Indexed: 12/25/2022]
Affiliation(s)
- Kai Sheng Saw
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
| | - Jason Robertson
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
| | - Michael Walsh
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
| | - Phillip Hider
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
- Department of Population HealthUniversity of Otago Christchurch New Zealand
| | - Michael Rodgers
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
| | - Michael Booth
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
| | - Sanket Srinivasa
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
| | - Jonathan Koea
- Upper Gastrointestinal Unit, Department of SurgeryNorth Shore Hospital Auckland New Zealand
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20
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Peng Y, Wang L, Wu L, Zhang L, Nie G, Guo M. Methylation of SLFN11 promotes gastric cancer growth and increases gastric cancer cell resistance to cisplatin. J Cancer 2019; 10:6124-6134. [PMID: 31762822 PMCID: PMC6856579 DOI: 10.7150/jca.32511] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Accepted: 08/20/2019] [Indexed: 02/06/2023] Open
Abstract
Background and Aim: Human SLFN11 gene encodes a protein with structural similarity to RNA helicases, which was reported to sensitize cancer cells to DNA-damaging agents. This study explored the epigenetic regulation and mechanism of SLFN11 in human gastric cancer. Methods: Eight human gastric cancer cell lines and 201 cases of primary gastric cancer were analyzed. Methylation specific PCR, flow cytometry, xenograft mouse model and siRNA technique were employed. Results: SLFN11 was methylated in 29.9% (60/201) of primary gastric cancer. The expression of SLFN11 was regulated by promoter region methylation. Methylation of SLFN11 was significantly associated with tumor size (p < 0.05). SLFN11 suppressed gastric cancer growth both in vitro and in vivo and enhanced the ability of cisplatin to induce S-phrase arrest and apoptosis in gastric cancer cells. Conclusions: SLFN11 is frequently methylated in human gastric cancer, and its expression is regulated by promoter region methylation. Our results demonstrate that SLFN11 is a tumor suppressor in human gastric cancer, and methylation of SLFN11 may serve as a cisplatin resistant marker in human gastric cancer.
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Affiliation(s)
- Yaojun Peng
- Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China
| | - Li Wang
- Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, #127 Dongming Road, Zhengzhou, Henan Province 450008, China
| | - Liangliang Wu
- Department of Oncology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China
| | - Ling Zhang
- Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, #127 Dongming Road, Zhengzhou, Henan Province 450008, China
| | - Guangjun Nie
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, North Road No. 1, Zhongguancun, Beijing, 100190, China
| | - Mingzhou Guo
- Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China
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Li J, Tong G, Huang C, Luo Y, Wang S, Zhang Y, Cheng B, Zhang Z, Wu X, Liu Q, Li M, Li L, Ni B. HOXC10 promotes cell migration, invasion, and tumor growth in gastric carcinoma cells through upregulating proinflammatory cytokines. J Cell Physiol 2019; 235:3579-3591. [PMID: 31552684 DOI: 10.1002/jcp.29246] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 09/03/2019] [Indexed: 12/25/2022]
Affiliation(s)
- Jingzhang Li
- Department of Oncology, Liuzhou People's Hospital The Affiliated Liuzhou People's Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Gangling Tong
- Department of Oncology, Shenzhen Hospital Peking University Shenzhen Guangdong China
| | - Cheng Huang
- Department of Oncology, Liuzhou People's Hospital The Affiliated Liuzhou People's Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Yunsheng Luo
- Department of Gastrointestinal Surgery, Liuzhou People's Hospital The Affiliated Liuzhou People’ Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Shubin Wang
- Department of Oncology, Shenzhen Hospital Peking University Shenzhen Guangdong China
| | - Ying Zhang
- Department of Pathology, Liuzhou People's Hospital The Affiliated Liuzhou People’ Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Boran Cheng
- Department of Oncology, Shenzhen Hospital Peking University Shenzhen Guangdong China
| | - Zhihong Zhang
- Department of Oncology, Liuzhou People's Hospital The Affiliated Liuzhou People's Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Xuan Wu
- Department of Oncology, Shenzhen Hospital Peking University Shenzhen Guangdong China
| | - Qiumei Liu
- Department of Oncology, Liuzhou People's Hospital The Affiliated Liuzhou People's Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Min Li
- Department of Oncology, Liuzhou People's Hospital The Affiliated Liuzhou People's Hospital of Guangxi Medical University Liuzhou Guangxi China
| | - Laiqing Li
- Department of Scientific Research Guangzhou Youdi Bio‐Technology Co., Ltd. Guangzhou Guangdong China
| | - Bingqiang Ni
- Department of Oncology, Liuzhou People's Hospital The Affiliated Liuzhou People's Hospital of Guangxi Medical University Liuzhou Guangxi China
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Liu F, Fan Z, Song N, Han M, Yan M, Guo LH, Jihui J, Liu S. XRCC4, which is inhibited by PFDA, regulates DNA damage repair and cell chemosensitivity. J Cell Biochem 2019; 120:12665-12676. [PMID: 30834581 DOI: 10.1002/jcb.28534] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/17/2019] [Accepted: 01/24/2019] [Indexed: 12/27/2022]
Abstract
The mechanism of environmental pollution promoting gastric cancer incidence and difficulty of treatment is not fully understood. In the present article, perfluorodecanoic acid (PFDA), a common persistent environmental pollutant, was used to treat the gastric cell lines and mice to test its genotoxicity. The γ-H2AX immunoblot and plasmid fragment PCR results showed that PFDA had a promotion effect on the DNA double-strand breaks (DSBs) in human and mouse cells. Subsequent results showed that PFDA significantly altered the sensitivity of cells to chemotherapy. Microarray data showed that the expressions of some important DNA repair genes were changed. Further investigation discovered that PFDA inhibition of DNA repair was mediated by X-ray repair cross complementing 4 (XRCC4). The cells deficient in XRCC4 generally exhibited reduced proliferation and premature aging in culture; however, our results indicated that PFDA induced p53 inhibition rescued cells from the apoptosis that was triggered by nonhomologous end-joining (NHEJ) inactivation, and overexpression of p53 expression in PFDA-treated cells enhanced their apoptosis. Finally, T-cell specific factor 4 was suggested by the results as an upstream regulator of XRCC4. This article revealed for the first time that perfluorinated chemicals affect chemotherapeutic sensitivity and the NHEJ pathway, and p53 reduction rescues cells from death.
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Affiliation(s)
- Fengyan Liu
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China.,Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Ziyan Fan
- China National Tobacco Quality Supervision & Test Center, Zhengzhou, Henan, China
| | - Ning Song
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
| | - Mingyong Han
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China.,Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Ming Yan
- Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Liang-Hong Guo
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China
| | - Jia Jihui
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
| | - Shili Liu
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
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23
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Karamitabar A, Shahali S, Dadgo M, Mansor Sohani S, Ghorbanpour A, Abrishamkarzadeh H, Jaafary H, Mirbehresi P. The Effect of Kinesio Tape on Knee Pain and Quality of Life in Subjects with Knee Osteoarthritis – A Randomized Clinical Trial. FUNCTION AND DISABILITY JOURNAL 2019. [DOI: 10.30699/fdisj.1.4.27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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24
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Zarean E, Amini P, Yaseri M, Hajihosseini M, Azimi T, Mahmoudi M. Determining Risk Factors for Gastric and Esophageal Cancers between 2009-2015 in East-Azarbayjan, Iran Using Parametric Survival Models. Asian Pac J Cancer Prev 2019; 20:443-449. [PMID: 30803206 PMCID: PMC6897034 DOI: 10.31557/apjcp.2019.20.2.443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Esophageal cancer (EC) and Gastric cancer (GC) have been identified as two of the most common
cancers in the northeastern regions of Iran. The increasing rates of these types of cancers requires attention. This study
aims to assess the potential risk factors for these two cancers and then determine shared risk factors between them
in a population of Iranian patients using parametric survival models. Methods: This retrospective cohort study was
conducted using 127 patients with EC and 184 patients with GC in East Azarbaijan, Iran who were diagnosed and
registered during the years 2009-2010 in Iran’s National Cancer Control Registration Program and were followed for
five years. Parametric survival models were used to find the risk factors of the patients. Akaike Information Criteria was
used to identify the best parametric model in this study. Interaction analysis was used to determine shared risk factors
between EC and GC. Results: The mean (±standard deviation) age of diagnoses for EC and GC were 66.92(±11.95) and
66.5(±11.5) respectively. The survival time ranges of GC patients was (0.07-70.33) and the survival time ranges were
from 0.10 to 69.03 months for EC patients. Multivariable Log- logistic model showed that being married (OR=2.25, 95%
CI: 1.33 - 3.81) for EC patients and Esophagectomy surgery for EC (OR: 1.62, 95% CI: 1.04 – 2.55) and GC (OR: 1.60,
95% CI: 1.02 – 2.53) had significant effects on survival. Age at the time of diagnosis, job status, and Esophagectomy
surgery were statistically comparable regarding their magnitude of effect on survival of two cancers (all Ps>0.05).
Conclusion: Esophagectomy surgery and being married were important risk factors in EC and GC. The log-logistic
model was the most appropriate statistical approach to identify significant risk factors on survival of both cancers.
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Affiliation(s)
- Elaheh Zarean
- Modeling in Health Research Center, School of Public Health, Department of Epidemiology and Biostatistics, Shahrekord University of Medical Sciences, Shahrekord, Iran.
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25
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Wang X, Jiang X, Zhou L, Wang Z, Huang H, Wang M. LncRNA‑NEF is involved the regulation of gastric carcinoma cell proliferation by targeting RUNX1. Mol Med Rep 2019; 19:2051-2056. [PMID: 30664208 DOI: 10.3892/mmr.2019.9869] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 10/26/2018] [Indexed: 11/06/2022] Open
Abstract
Neighboring enhancer of FOXA2 (NEF) is a newly discovered long non‑coding RNA (lncRNA) that serves an oncogenic function in the metastasis of hepatocellular carcinoma, while its involvement in other types of cancer and in tumor cell proliferation remain unknown. In the present study, tumor tissues and adjacent healthy tissues were obtained from patients with gastric carcinoma, and blood was extracted from patients with gastric carcinoma and healthy controls. Expression of NEF in those tissues was detected using a reverse transcription‑quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of serum lncRNA NEF for gastric carcinoma. All patients were followed‑up for 5 years following discharge, and survival curves were plotted to evaluate the diagnostic value of serum lncRNA‑NEF for gastric carcinoma. LncRNA‑NEF overexpression and small interfering RNA (siRNA) silencing cell lines were established and the effects on cell proliferation and runt‑related transcription factor 1 (Runx1) expression were detected using a Cell Counting Kit‑8 assay and western blot analysis, respectively. It was revealed that NEF was significantly downregulated in tumor tissues compared with in adjacent tissues. Levels of circulation NEF in serum were lower in patients with gastric carcinoma compared with in healthy controls, and were decreased with the increasing stages of primary tumor. Serum NEF is a sensitive diagnostic and prognostic marker for gastric carcinoma. NEF siRNA silencing promoted, and overexpression inhibited, gastric carcinoma proliferation. In addition, NEF overexpression promoted, and NEF siRNA silencing inhibited, Runx1 expression. Therefore, it was concluded that lncRNA NEF may participate in the regulation of cancer cell proliferation by regulating Runx1 expression.
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Affiliation(s)
- Xue Wang
- Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China
| | - Xue Jiang
- Department of Dermatology, Chongqing First People's Hospital, Chongqing 400011, P.R. China
| | - Li Zhou
- Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China
| | - Zhuo Wang
- Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China
| | - He Huang
- Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China
| | - Mengqiao Wang
- Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China
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26
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Zhang Z, Fan B, Liu F, Song N, Peng Y, Ma W, Ma R, Dong T, Liu S. HOX transcript antisense RNA is elevated in gastric carcinogenesis and regulated by the NF-κB pathway. J Cell Biochem 2019; 120:10548-10555. [PMID: 30635945 DOI: 10.1002/jcb.28340] [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: 08/28/2018] [Accepted: 11/29/2018] [Indexed: 01/17/2023]
Abstract
The expression pattern of HOX transcript antisense RNA (HOTAIR) in the progression of gastric cancer and the regulation of its expression are still unclear. In the current study, HOTAIR expressions in gastric tissues collected from patients with superficial gastritis, atrophic gastritis, atypical hyperplasia, and gastric cancer as well as normal controls was quantitatively examined. The results showed that the expression of HOTAIR was higher in gastric cancer than in normal tissues, but reached the highest level in atrophic gastritis, suggesting that HOTAIR may be involved in the molecular process of nonresolving inflammation. Then tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a known gene associated with nonresolving inflammation, was overexpressed and the results showed that the promotion in TIPE2 expression triggered HOTAIR reduction, this result was further verified by microarray analysis and TIPE2 knockout mice. Subsequently, the data obtained from HOTAIR knockdown experiment showed that it significantly enhanced colony forming capability and inhibited p27 expression in AGS cells. Furthermore, deletion constructs and luciferase-based activity assays indicated that the -475 to -443bp region of HOTAIR promoter contained a crucial regulatory element. Transcription factor prediction with software TRANSFAC revealed that nuclear factor-κB signaling protein p65 had a binding site in this region and might have roles in HOTAIR expression. The binding of phosphor-p65 to HOTAIR promoter was verified by chromatin immunoprecipitation, and succeeding experiment results demonstrated that p65 reduction by p65 small interfering RNA and TIPE2 overexpression also decreased HOTAIR expression. Conclusively, our results suggest that HOTAIR was associated with nonresolving inflammation, and its expression is regulated by p65.
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Affiliation(s)
- Zhun Zhang
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China.,Department of Breast Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Bingbing Fan
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
| | - Fengyan Liu
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China.,Department of Gastroenterology Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Ning Song
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
| | - Yanping Peng
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
| | - Wenzheng Ma
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
| | - Rongtao Ma
- Department of Burn, Linqu County People's Hospital, Weifang, Shandong, China
| | - Tianyi Dong
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China.,Department of Breast Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Shili Liu
- Department of Medical Microbiology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China
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27
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Disruption of the Tff1 gene in mice using CRISPR/Cas9 promotes body weight reduction and gastric tumorigenesis. Lab Anim Res 2018; 34:257-263. [PMID: 30671113 PMCID: PMC6333602 DOI: 10.5625/lar.2018.34.4.257] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/07/2018] [Accepted: 12/08/2018] [Indexed: 01/27/2023] Open
Abstract
Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. TFF1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated TFF1-knockout (KO) mice, without a neomycin resistant (NeoR) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our TFF1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established TFF1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that TFF1 expression influences gender differences.
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28
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Zhu X, Huang G, Jin P. Clinicopathological and prognostic significance of aberrant G protein-couple receptor 110 (GPR110) expression in gastric cancer. Pathol Res Pract 2018; 215:539-545. [PMID: 30638950 DOI: 10.1016/j.prp.2018.12.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 11/13/2018] [Accepted: 12/05/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND GPR110 is a member of the adhesion G protein-coupled receptor family, which has been identified as an oncogene in various cancers, including hepatocellular carcinoma, lung cancer, prostatic cancer and glioma. Whereas the expression and the clinical relevance of GPR110 in gastric cancer has not been investigated. The research purpose of this study was to explore the expression pattern of GPR110 and evaluate its clinical-pathological and prognostic value in gastric cancer. METHODS In this study, the expression of GPR110 was detected in 117 paired gastric cancer tissues and adjacent non-tumorous tissues by using qRT-PCR and immunohistochemical assays. Univariate Kaplan-Meier and multivariate Cox analysis were used to determine the prognostic value of GPR110 in GC. RESULTS We demonstrated that the mRNA and protein levels of GPR110 in GC tissues were overexpressed than the adjacent non-tumorous tissues. Furthermore, elevated GPR110 protein expression was correlated with decreased overall and recurrence-free survival (P = 0.001 and P = 0.000, respectively). Univariate and multivariate analysis indicated that GPR110 protein level may serve as an independent prognostic indicator for determining prognosis of GC patients. CONCLUSIONS Our study revealed that high expression of GPR110 predicts the poor prognosis of GC patients, and GPTR110 may function as a potential biomarker for the diagnosis of GC.
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Affiliation(s)
- Xiaolian Zhu
- Department of Medical Oncology, Zhuji People's Hospital of Zhejiang Province, 9 Jianmin Road, Taozhu street, Zhuji, Shaoxing, Zhejiang, China
| | - Guoqiang Huang
- Department of General Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, China
| | - Pengfei Jin
- Department of Gastrointestinal Surgery, The Affiliated Wenling Hospital of Wenzhou Medical University, The First People's Hospital of Wenling, Taizhou, China.
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29
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Chen C, Fu YH, Li MH, Ruan LY, Xu H, Chen JF, Zhao WL, Meng HH, Xing YX, Hong W, Wang JS. Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis. J Pharm Biomed Anal 2018; 164:231-240. [PMID: 30391812 DOI: 10.1016/j.jpba.2018.10.035] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 08/02/2018] [Accepted: 10/21/2018] [Indexed: 12/18/2022]
Abstract
Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.
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Affiliation(s)
- Cheng Chen
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Yong-Hong Fu
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Ming-Hui Li
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Ling-Yu Ruan
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Han Xu
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Jian-Feng Chen
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Wen-Long Zhao
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Hui-Hui Meng
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Yue-Xiao Xing
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Wei Hong
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Jun-Song Wang
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
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30
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Zhang Z, Kong Y, Yang W, Zhang B, Ma F, Liu H, Hua Y. MicroRNA-218 enhances gastric cancer cell cisplatin sensitivity by targeting survivin. Exp Ther Med 2018; 16:4796-4802. [PMID: 30542435 DOI: 10.3892/etm.2018.6802] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 06/08/2018] [Indexed: 12/19/2022] Open
Abstract
Gastric cancer (GC) is one of the most prevalent types of cancer worldwide. Cisplatin based chemotherapy is the primary strategy implemented for the treatment of G; however, chemoresistance is a major problem. Previous studies have indicated that microRNAs (miRs) are associated with chemoresistance in various types of cancer and that miR-218 specifically, serves important roles in the growth of GC cells. The present study assessed the potential biological roles of miR-218 in GC cell cisplatin (DDP) resistance. The results obtained from a polymerase chain reaction assay indicated that the expression of miR-218 was decreased in cisplatin resistant SGC7901/DDP cells compared with SGC7901 cells. Furthermore, MTT results indicated that the upregulation of miR-218 expression significantly enhanced SGC7901/DDP cell sensitivity to DDP. The results of a dual-luciferase assay indicated that survivin was a direct target gene of miR-218. Results also demonstrated that miR-218 was overexpressed in SGC7901/DDP cells and that the downregulation of survivin expression enhanced SGC7901/DDP cell sensitivity to DDP. Further study demonstrated that the upregulation of miR-218 decreased the expression of survivin in SGC7901/DDP cells and induced apoptosis. The findings of the present study indicated that the induction of miR-218 enhanced GC cell DDP resistance via the regulation of survivin, which may potentially benefit the clinical treatment of GC in the future.
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Affiliation(s)
- Zhandong Zhang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Ye Kong
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Wei Yang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Bin Zhang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Fei Ma
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Hongxing Liu
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yawei Hua
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
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31
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Yu X, Zheng H, Tse G, Zhang L, Wu WKK. CASC2: An emerging tumour-suppressing long noncoding RNA in human cancers and melanoma. Cell Prolif 2018; 51:e12506. [PMID: 30094876 DOI: 10.1111/cpr.12506] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 06/08/2018] [Indexed: 12/16/2022] Open
Abstract
Deregulation of long noncoding RNAs (lncRNAs) has been implicated in tumourigenesis. Cancer Susceptibility Candidate 2 (CASC2) is a lncRNA downregulated in multiple cancer types, including endometrial, lung, gastric and colorectal cancers. CASC2 functions as a tumour-suppressive lncRNA though multiple mechanisms, such as sequestration of oncogenic microRNAs and repression of Wnt/β-catenin signalling. Pertinent to clinical practice, the use of CASC2 as a prognostic marker has been demonstrated in sporadic studies. These findings suggested that CASC2 might play an important role in human cancers and melanoma. More efforts are warranted to examine the function role of CASC2 in other cancer types. Further validation is also needed to promote its development to be a clinically utilizable prognostic biomarker.
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Affiliation(s)
- Xin Yu
- Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Heyi Zheng
- Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gary Tse
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Lin Zhang
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - William Ka Kei Wu
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key Laboratory of Digestive Disease and LKS Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
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32
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Yamamoto M, Shimokawa M, Kawano H, Ohta M, Yoshida D, Minami K, Ikebe M, Morita M, Toh Y. Benefits of laparoscopic surgery compared to open standard surgery for gastric carcinoma in elderly patients: propensity score-matching analysis. Surg Endosc 2018; 33:510-519. [DOI: 10.1007/s00464-018-6325-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 07/06/2018] [Indexed: 02/06/2023]
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33
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Hsu WH, Kuo CH, Wu MC, Su YC, Chen CY, Wang JY, Shih HY, Lu CY, Wu DC, Yu FJ. Application of miniprobe sonography in the local staging of earlier stage upper gastrointestinal epithelial neoplasm: A four-year experience in a single center. ADVANCES IN DIGESTIVE MEDICINE 2018. [DOI: 10.1002/aid2.13076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Meng-Chieh Wu
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Yu-Chung Su
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Chiao-Yun Chen
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Jaw-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Hsiang-Yao Shih
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Chien-Yu Lu
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
| | - Fang-Jung Yu
- Division of Gastroenterology, Department of Internal Medicine; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
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34
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Quintana M, Toriz JA, Novick D, Jones K, Botello BS, Silva JA. Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review. PHARMACOECONOMICS - OPEN 2018; 2:191-201. [PMID: 29623621 PMCID: PMC5972114 DOI: 10.1007/s41669-017-0043-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
BACKGROUND Little evidence is available on the management and cost of treating patients with advanced or metastatic gastric cancer (GC). This study evaluates patient characteristics, treatment patterns, and resource utilization for these patients in Mexico. METHODS Data were collected from three centers of investigation (tertiary level). Patients were ≥18 years of age, diagnosed between 1 January 2009 and 1 January 2015, had advanced or metastatic GC, received first-line fluoropyrimidine/platinum, and had ≥3 months follow-up after discontinuing first-line treatment. Data were summarized using descriptive statistics. RESULTS The study sample totaled 180. Patients' mean age was 57.2 years (±12.4) and 57.0% were male; 151 (83.9%) patients received second-line chemotherapy. A total of 16 and 19 regimens were identified in first- and second-line therapy. Of the sample, 51 (28.3%) received third-line therapy, and <10% received more than three lines of active chemotherapy. Supportive care received in first- and second-line chemotherapy, included pain interventions (12.2 and 7.9%), nutritional support (3.3 and 1.3%), radiotherapy (6.1 and 16.6%), and transfusions (13.3 and 10.6%), respectively. Using Mexican Institute of Social Security (IMSS) tariffs, the average total cost per patient-month in first- and second-line therapy was US$1230 [95% confidence interval (CI) 1034-1425] and US$1192 (95% CI 913-1471), respectively. Administration and acquisition of chemotherapy comprised the majority of costs. CONCLUSIONS This study shows considerable variation in first- and second-line chemotherapy regimens of patients with advanced or metastatic GC. Understanding GC treatment patterns in Mexico will help address unmet needs.
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Affiliation(s)
- Miguel Quintana
- Department of Medical Oncology, Hospital de Oncología, Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - José A Toriz
- Department of Medical Oncology, Hospital de Oncología, Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | - Kyla Jones
- Tecnología e Información para la Salud, Mexico City, Mexico
| | | | - Juan Alejandro Silva
- Department of Medical Oncology, Hospital de Oncología, Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
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Yahyapour R, Amini P, Rezapour S, Cheki M, Rezaeyan A, Farhood B, Shabeeb D, Musa AE, Fallah H, Najafi M. Radiation-induced inflammation and autoimmune diseases. Mil Med Res 2018; 5:9. [PMID: 29554942 PMCID: PMC5859747 DOI: 10.1186/s40779-018-0156-7] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 03/02/2018] [Indexed: 12/22/2022] Open
Abstract
Currently, ionizing radiation (IR) plays a key role in the agricultural and medical industry, while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern. Exposure to IR has various detrimental effects on normal tissues. Although an increased risk of carcinogenesis is the best-known long-term consequence of IR, evidence has shown that other diseases, particularly diseases related to inflammation, are common disorders among irradiated people. Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people. Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR. However, the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated, and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role. Thus, cytokines, including interleukin-1(IL-1), tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to IR. Additionally, these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH). It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster. In the present study, we reviewed the evidence of radiation-induced diabetes and thyroid diseases, as well as the potential roles of inflammatory responses. In addition, we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.
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Affiliation(s)
- Rasoul Yahyapour
- School of Medicine, Jiroft University of Medical Sciences, Jiroft, Zip code: 8813833435, Iran
| | - Peyman Amini
- Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Zip code: 1417613151, Iran
| | - Saeed Rezapour
- Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Zip code: 1417613151, Iran
| | - Mohsen Cheki
- Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Zip code: 6135715794, Iran
| | - Abolhasan Rezaeyan
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Zip code: 1449614535, Iran
| | - Bagher Farhood
- Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Zip code: 3715835155, Iran
| | - Dheyauldeen Shabeeb
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences (International Campus), Tehran, Zip code: 1417613151, Iran.,Department of Physiology, College of Medicine, University of Misan, Misan, Iraq
| | - Ahmed Eleojo Musa
- Research center for molecular and cellular imaging, Tehran University of Medical Sciences, Tehran, Zip code: 1417613151, Iran
| | - Hengameh Fallah
- Department of Chemistry, Faculty of Science, Islamic Azad University, Arak, Zip code: 3836119131, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Zip code: 6714869914, Iran.
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Yu X, Hu F, Li C, Yao Q, Zhang H, Xue Y. Clinicopathologic characteristics and prognosis of proximal and distal gastric cancer. Onco Targets Ther 2018. [PMID: 29520154 PMCID: PMC5833755 DOI: 10.2147/ott.s157378] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Background and objectives The dismal prognosis of gastric cancer patients is a global problem. We aim to evaluate the clinicopathologic features and prognostic factors of proximal and distal gastric cancer. Materials and methods Gastric cancer cases diagnosed and treated at the same surgical unit between 2007 and 2010 were reviewed. Follow-up data from all patients were collected for at least 5 years until 2015. A total of 964 patients were studied (distal gastric cancer [DG], n=777 and proximal gastric cancer [PG], n=187). Results DG patients had a relatively higher percentage of females, more thorough therapy (R0 [D0/D1/D2]), fewer combined organ resections, younger age, smaller tumors (<5 cm), shorter surgery durations, less blood loss during surgery, and a relatively lower percentage of nodal metastases and a TNM stage of 4 (p<0.05). A significantly higher 5-year survival rate was observed in DG patients compared to PG patients (DG: 51%, PG: 28%; p<0.001). A multivariate analysis demonstrated that tumor size, blood loss during surgery, surgery approach of lymph node dissection, treatment with palliative surgery, histopathologic type, TNM stage, and tumor location were independent predictors of poor outcome. Conclusion The different characteristics and prognosis of DG and PG cases have implications for the development of guiding strategies for a surgical program and assessment of prognosis of gastric cancer patients based on tumor location.
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Affiliation(s)
- Xuefeng Yu
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
| | - Fulan Hu
- Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, China
| | - Chunfeng Li
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
| | - Qiang Yao
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
| | - Hongfeng Zhang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
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Inghelmann R, Grande E, Francisci S, Verdecchia A, Micheli A, Baili P, Capocaccia R, De Angelis R. Regional Estimates of Stomach Cancer Burden in Italy. TUMORI JOURNAL 2018; 93:367-73. [PMID: 17899867 DOI: 10.1177/030089160709300407] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aims and background Stomach cancer still remains one of the most frequent tumors in Italy and Europe. The aim of this paper is to present estimates for stomach cancer mortality, incidence and prevalence over the period 1970-2010 for the Italian regions and for Italy as a whole. Methods Estimated figures for incidence, prevalence and mortality were obtained by using the MIAMOD method. Starting from the knowledge of mortality in the period 1970-1999 and of relative survival in the period of diagnosis 1978-1994, we derived incidence and prevalence estimates and projections up to the year 2010 by means of a statistical back-calculation approach. Survival at the regional and national levels was modelled on the basis of published survival data from the Italian cancer registries. Results Incidence and mortality trends for both sexes decrease by about 60% during the estimation period 1970-2010. Both indicators show a 2-fold male/female ratio all over the country, and a similar gender time trend. The incidence and mortality in the North and Center of the country are estimated to be higher and to decrease more steeply than those in the South, both for men and women. A total of around 13,000 incident cases, 57,000 prevalent cases, and 8,000 deaths are estimated to have occurred in Italy in 2005. Conclusions The incidence and mortality trends are estimated to decline during the entire period 1970-2010, with different slopes between northern-central and southern regions. The incidence and mortality are quite similar among Italian regions, showing that the risk of developing the disease diminishes and is becoming more homogeneous than in the past decades all over the country.
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Affiliation(s)
- Riccardo Inghelmann
- Reparto di Epidemiologia dei Tumori, Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità, Rome, Italy
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Li D, Ding J, Wang X, Wang C, Wu T. Fibronectin Promotes Tyrosine Phosphorylation of Paxillin and Cell Invasiveness in the Gastric Cancer Cell Line AGS. TUMORI JOURNAL 2018; 95:769-79. [DOI: 10.1177/030089160909500621] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Aims and Background Paxillin is a central protein within the focal adhesion and serves as a critical transducer of signals from fibronectin. Although abnormal expression of fibronectin and paxillin is often observed during the development of human malignancies, the relationship between paxillin and cell invasion in gastric cancer is still unclear. The current study was designed to investigate the potential role and mechanisms of fibronectin in tyrosine phosphorylation of paxillin and in the invasiveness of gastric cancer cells. Methods Expression of paxillin in human gastric cancer samples was examined by immunohistochemical staining. A gastric cancer cell line, AGS, was stimulated by fibronectin with gradient concentrations, and expression of paxillin and phosphorylation of paxillin tyrosine 118 (tyr118) was detected by immunoprecipitation and Western blotting. The invasiveness of AGS cells was measured by the modified Boyden chamber assay. Small interfering RNA (siRNA) targeting paxillin was used to establish the role of paxillin (tyr118) in the process of cell invasion enhanced by fibronectin. siRNA targeting focal adhesion kinase (FAK) was used to verify the effect of FAK tyrosine 397 (tyr397) on phosphorylation of paxillin(tyr118). Results Positivity for paxillin staining in human gastric cancer was associated with tumor stage. AGS cell showed dose dependence on fibronectin for invasiveness and phosphorylation of paxillin (tyr118). Invasiveness and phosphorylation of paxillin(tyr118) in AGS cells reached their peak when the concentration of fibronectin reached 100 nmol/L. siRNA targeting paxillin decreased the phosphorylation of paxillin(tyr118) and the invasiveness of AGS cells significantly as compared with controls. Blockage of FAK(tyr397) can inhibit phosphorylation of paxillin(tyr118) stimulated by fibronectin. Conclusions Fibronectin promotes paxillin(tyr118) phosphorylation and invasiveness of AGS cells. Paxillin silencing by RNA interference inhibits the cell invasiveness stimulated by fibronectin. Paxillin is a key factor in the fibronectin-stimulated invasiveness of AGS cells.
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Affiliation(s)
- Dan Li
- Digestive Department, the First Affiliated Hospital of Fujian Medical University
| | - Jian Ding
- Digestive Department, the Union Hospital of Fujian Medical University, Fuzhou, Fujian, China. Dan Li and Jian Ding contributed equally to this research
| | - Xiaozhong Wang
- Digestive Department, the First Affiliated Hospital of Fujian Medical University
| | - Chengdang Wang
- Digestive Department, the Union Hospital of Fujian Medical University, Fuzhou, Fujian, China. Dan Li and Jian Ding contributed equally to this research
| | - Ting Wu
- Digestive Department, the Union Hospital of Fujian Medical University, Fuzhou, Fujian, China. Dan Li and Jian Ding contributed equally to this research
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García I, del Casar JM, Corte MD, Allende MT, García-Muñiz JL, Vizoso F. Epidermal Growth Factor Receptor and c-erbB-2 Contents in Unresectable (UICC R1 or R2) Gastric Cancer. Int J Biol Markers 2018; 18:200-6. [PMID: 14535591 DOI: 10.1177/172460080301800308] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Epidermal growth factor receptor (EGFR) and c-erbB-2 are membrane receptors expressed in a variety of solid human cancers and directly correlated with poor prognosis. The objective of this work was to evaluate the EGFR and c-erbB-2 levels in non-resectable gastric carcinomas, their possible relationship with a variety of clinicopathological tumor parameters, and their prognostic significance. Methods This was a prospective analysis of 65 patients with unresectable gastric carcinomas (UICC R1 or R2), who underwent palliative surgery and were followed up for a median period of 13 months. Membranous EGFR levels were examined by radioligand binding assays and cytosolic c-erbB-2 levels by means of an immunoenzymatic assay. Results There was a wide variability in EGFR (80.3-2910 fmol/mg of protein) and c-erbB-2 (0.4-10071 NHU/mg of protein) levels in neoplastic tissues from patients with unresectable gastric carcinomas. Median c-erbB2 was significantly higher in tumors of the intestinal type than in tumors of the diffuse type (p=0.035) and in R2 than in R1 tumors (p=0.016). Statistical analysis showed that there was no relationship between tumor c-erbB-2 or EGFR content and any other patient or tumor characteristics. However, high levels of EGFR were significantly associated with a shorter overall survival (p=0.01). Conclusion Our data suggest a role of both transmembrane proteins in the progression of gastric cancer. EGFR and c-erbB-2 contents in unresectable gastric cancer could be utilized as appropriate biological markers for selecting candidates for treatment based on EGFR and/or c-erbB-2 inhibition.
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Affiliation(s)
- I García
- Servicio de Cirugía General, Hospital Central de Asturias, Oviedo, Spain
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Castro F, Shahal D, Tarajia M, Velásquez IM, Causadias MT, Herrera V, Gómez B, Cukier M, Motta J. Baseline characteristics, survival and direct costs associated to treatment of gastric cancer patients at the National Oncology Institute of Panama from 2012 to 2015: a hospital-based observational study. BMJ Open 2017; 7:e017266. [PMID: 28947456 PMCID: PMC5623512 DOI: 10.1136/bmjopen-2017-017266] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES Comprehensive epidemiological and economic studies of gastric cancer (GC) in Panama are limited. This study aims to evaluate the association between socioeconomic and clinical variables with survival, describe the survival outcomes according to clinical stage and estimate the direct costs associated to GC care in a Panamanian population with GC. DESIGN AND SETTING A retrospective observational study was conducted at the leading public institution for cancer treatment in Panama. PARTICIPANTS Data were obtained from 611 records of patients diagnosed with gastric adenocarcinoma (codes C16.0-C16.9 of the International Classification of Diseases 10th revision), identified between 1 January 2012 and 31 December 2015. METHODS Cox proportional hazards models were used to calculate HRs with 95% CI to examine associations between the variables and survival. Kaplan-Meier curves were used to assess overall and stage-specific survival. Direct costs (based on 2015 US$) were calculated per patient using standard costs provided by the institution for hospital admission (occupied bed-days), radiotherapy, surgery and chemotherapy, yielding total and overall mean costs (OMC). A comparison of OMC between groups (sex, social security status, clinical stage) was performed applying the bootstrap method with a t-test of unequal variances. RESULTS An increased risk of dying was observed for patients without social security coverage (HR: 2.02; 95% CI 1.16 to 3.53), overlapping tumours (HR: 1.50; 95% CI 1.02 to 2.22), poorly differentiated tumours (HR: 2.27; 95% CI 1.22 to 4.22) and stage IV disease (HR: 5.54; 95% CI 3.38 to 9.08) (adjusted models). Overall 1-year survival rate was 41%. The estimated OMC of GC care per patient was 4259 US$. No statistically significant differences were found in OMC between groups. CONCLUSIONS Socioeconomic disparities influence GC outcomes and healthcare utilisation. Policies addressing healthcare disparities related to GC are needed, as well as in-depth studies evaluating barriers of access to GC-related services.
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Affiliation(s)
- Franz Castro
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - David Shahal
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - Musharaf Tarajia
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - Ilais Moreno Velásquez
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - Maribel Tribaldos Causadias
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - Víctor Herrera
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - Beatriz Gómez
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
| | - Moisés Cukier
- Division of Surgical Oncology, National Oncology Institute, Panama City, Panama
| | - Jorge Motta
- Department of Research and Health Technology Assessment, Gorgas Memorial Institute for Health Studies, Panama City, Panama
- National Secretariat for Science and Technology, Panama City, Panama
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Asghari MH, Moloudizargari M, Ghobadi E, Fallah M, Abdollahi M. Melatonin as a multifunctional anti-cancer molecule: Implications in gastric cancer. Life Sci 2017; 185:38-45. [DOI: 10.1016/j.lfs.2017.07.020] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 07/14/2017] [Accepted: 07/20/2017] [Indexed: 12/13/2022]
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Klameth L, Rath B, Hamilton G. In vitro Cytotoxic Activities of the Oral Platinum(IV) Prodrug Oxoplatin and HSP90 Inhibitor Ganetespib against a Panel of Gastric Cancer Cell Lines. J Cancer 2017; 8:1733-1743. [PMID: 28819369 PMCID: PMC5556635 DOI: 10.7150/jca.17816] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 04/01/2017] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer exhibits a poor prognosis and is the third most common cause of cancer death worldwide. Chemotherapy of metastatic gastric cancer is based on combinations of platinum drugs and fluoropyrimidines, with added agents. Oxoplatin is a stable oral platinum(IV) prodrug which is converted to a highly active tetrachlorido(IV) complex under acidic conditions. In the present work, we studied the cytotoxic effects of oxoplatin against a panel of four gastric cancer cell lines in vitro. Furthermore, the role of HSP90 in chemoresistance of these lines was investigated using the specific inhibitor ganetespib. The KATO-III, MKN-1, MKN-28, MKN-45 lines were used in MTT chemosensitivity, cell cycle and apoptosis assays. KATO-III is a signet ring diffuse cell type, MKN-1 an adenosquamous primary, MKN-28 a well-differentiated intestinal type and the MKN-45 a poorly differentiated, diffuse type gastric carcinoma line. Cytotoxicity was tested in MTT assays and intracellular signal transduction with proteome profiler Western blot arrays. Interactions of platinum drugs and ganetespib were calculated with help of the Chou-Talalay method. The prodrug oxoplatin revealed low activity against the four gastric cancer cell lines, whereas the platinum tetrachlorido(IV) complex and cisplatin gave IC50 values of 1-3 µg/ml with increasing chemoresistance observed in the order of MKN-1, KATO-III, MKN-28 to MKN-45. With exception of KATO-III and MKN-28/oxoplatin, all other cell lines featured marked synergistic toxicity with clinically achievable concentrations of ganetespib. Oral administration of a platinum agent such as oxoplatin would be of great value for patients and care providers alike. These results suggest that the oncogene-stabilizing HSP90 chaperone represents an important mediator of chemoresistance in gastric cancer. Ganetespib reduced the phosphorylation of p53, Akt1/2/3 and PRAS40, as well as of WNK1, a kinase which regulates intracellular chloride concentrations. Intracellular chloride was reported to control proliferation of gastric cancer cell lines. Expression of MUC1 was not downregulated in contrast to the expression of CAIX, a prognostic marker in gastric cancer. In conclusion, the HSP90 inhibitor ganetespib synergizes with platinum anticancer drugs and modulates intracellular signal transduction in direction of a less proliferative and aggressive phenotype.
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Affiliation(s)
- Lukas Klameth
- Department for Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Barbara Rath
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Gerhard Hamilton
- Department of Surgery, Medical University of Vienna, Vienna, Austria
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Li Y, Hu X, Ding D, Zou Y, Xu Y, Wang X, Zhang Y, Chen L, Chen Z, Tan W. In situ targeted MRI detection of Helicobacter pylori with stable magnetic graphitic nanocapsules. Nat Commun 2017. [PMID: 28643777 PMCID: PMC5501158 DOI: 10.1038/ncomms15653] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori infection is implicated in the aetiology of many diseases. Despite numerous studies, a painless, fast and direct method for the in situ detection of H. pylori remains a challenge, mainly due to the strong acidic/enzymatic environment of the gastric mucosa. Herein, we report the use of stable magnetic graphitic nanocapsules (MGNs), for in situ targeted magnetic resonance imaging (MRI) detection of H. pylori. Several layers of graphene as the shell effectively protect the magnetic core from corrosion while retaining the superior contrast effect for MRI in the gastric environment. Boronic-polyethylene glycol molecules were synthesized and modified on the MGN surface for targeted MRI detection. In a mouse model of H. pylori-induced infection, H. pylori was specifically detected through both T2-weighted MR imaging and Raman gastric mucosa imaging using functionalized MGNs. These results indicated that enhancement of MRI using MGNs may be a promising diagnostic and bioimaging platform for very harsh conditions.
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Affiliation(s)
- Yunjie Li
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Ding Ding
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yuxiu Zou
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yiting Xu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Xuewei Wang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yin Zhang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Long Chen
- Faculty of Science and Technology, University of Macau, Av. da Universidade, Taipa 999078, Macau
| | - Zhuo Chen
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Weihong Tan
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China.,Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at Bio/nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200, USA
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Dong T, Feng Q, Liu F, Chang LK, Zhou X, Han M, Tian X, Zhong N, Liu S. Alteration of stomach microbiota compositions in the progression of gastritis induces nitric oxide in gastric cell. Exp Ther Med 2017; 13:2793-2800. [PMID: 28587343 PMCID: PMC5450739 DOI: 10.3892/etm.2017.4373] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 03/29/2017] [Indexed: 12/14/2022] Open
Abstract
Atrophic gastritis is considered to be an antecedent to intestinal metaplasia and gastric cancer. A previous study identified that Helicobacter pylori was absent at the severe atrophic gastritis stage, and alterations in the gastric microbial composition resembled those in gastric cancer. To explore the role of the bacteria absence of H. pylori in gastric carcinogenesis, in the current study, we compared the microbiota of clinically collected H. pylori-free gastric fluids from 30 patients with non-atrophic gastritis (N) and 22 patients with severe atrophic gastritis (S). We estimated the bacterial loads in the N and S groups by colony counting in culture agar as well as by measuring the concentration of the extracted DNA. The results showed a significant increase in bacterial load in patients with atrophic gastritis in comparison to non-atrophic gastritis. Then, we analyzed the microbial communities of the gastric fluids from all 52 patients using high-throughput sequencing of 16S rRNA amplicons. The Chao 1, Shannon and Simpson diversity indexes demonstrated that the bacterial richness and diversity were not significantly different between the N and S groups. Moreover, principal component analysis illustrated that the microbiomes from the S group were more scattered. Microbiota composition analysis showed that the entire dataset was clustered into 27 phyla, 61 classes, 106 orders, 177 families, 292 genera and 121 species. At the genus level, only the abundance of Prevotella was significantly different between the N and S groups. Further analysis showed that all the higher taxonomic categories were significantly different between the N and S groups. To assess the effects of the metabolic products of Prevotella spp. on gastric cell physiology, we treated the human gastric epithelial cell line AGS with acetic acid and monitored nitric oxide (NO) production. The results showed that acetic acid at low concentrations (0.5 and 5 µM) significantly inhibited AGS cells to secrete NO compared to phosphate buffer saline-treated control cells. These results suggest that the microbiota in non-atrophic gastritis may influence gastric epithelial cell physiology.
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Affiliation(s)
- Tianyi Dong
- Department of Medical Microbiology, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.,Department of Breast Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
| | - Qiang Feng
- Department of Human Microbiome, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250021, P.R. China
| | - Fengyan Liu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Lap Kam Chang
- Department of Medical Microbiology, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Xiangyu Zhou
- Department of Medical Microbiology, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Mingyong Han
- Department of Breast Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
| | - Xingsong Tian
- Department of Breast Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
| | - Ning Zhong
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Shili Liu
- Department of Medical Microbiology, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
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Li J, Gao J, Tian W, Li Y, Zhang J. Long non-coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR-1297. Cancer Cell Int 2017; 17:44. [PMID: 28396617 PMCID: PMC5383984 DOI: 10.1186/s12935-017-0408-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 03/06/2017] [Indexed: 01/02/2023] Open
Abstract
Background Emerging evidences have verified that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been found to be up-regulated in some human cancers. The main objective of this study was to investigate the expression level and biological function of MALAT1 in gastric cancer (GC). Methods Quantificational real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric carcinoma tissues and adjacent normal tissues, and the associations of MALAT1 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated. The HMGB2 mRNA and protein expressions were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was used to determine miR-1297 was a target of MALAT1. Results In this study, we demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal tissues and higher MALAT1 expression was correlated with local invasion, lymph node metastasis and TNM stage. Patients with higher MALAT1 expression predicted a shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted cells proliferation and invasion in GC. Mechanistically, our results demonstrated that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular sponging miR-1297, antagonizing its ability to suppress HMGB2 expression. Conclusions Taken together, these results demonstrated that MALAT1/miR-1297/HMGB2 axis acted as critical regulator pathway in GC tumorigenesis and progression, which provided a novel therapeutic target for gastric cancer.
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Affiliation(s)
- Jijun Li
- Department of Medical Oncology, Hebei Cang Zhou Central Hospital, No.16, Xinhuaxi Road, Cangzhou, Hebei 061000 China
| | - Jinghua Gao
- Department of Medical Oncology, Hebei Cang Zhou Central Hospital, No.16, Xinhuaxi Road, Cangzhou, Hebei 061000 China
| | - Wen Tian
- Department of Medical Oncology, Hebei Cang Zhou Central Hospital, No.16, Xinhuaxi Road, Cangzhou, Hebei 061000 China
| | - Yongsheng Li
- Department of Medical Oncology, Hebei Cang Zhou Central Hospital, No.16, Xinhuaxi Road, Cangzhou, Hebei 061000 China
| | - Jinghua Zhang
- Department of Medical Oncology, Hebei Cang Zhou Central Hospital, No.16, Xinhuaxi Road, Cangzhou, Hebei 061000 China
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Okada R, Naito M, Hattori Y, Seiki T, Wakai K, Nanri H, Watanabe M, Suzuki S, Kairupan TS, Takashima N, Mikami H, Ohnaka K, Watanabe Y, Katsuura-Kamano S, Kubo M, Hamajima N, Tanaka H. Matrix metalloproteinase 9 gene polymorphisms are associated with a multiple family history of gastric cancer. Gastric Cancer 2017; 20:246-253. [PMID: 27053167 DOI: 10.1007/s10120-016-0608-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 03/30/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. METHODS We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69 years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. RESULTS MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC (n = 23) and in individuals for whom one parent and their sibling(s) had a history of GC (n = 36) compared with those with no family history (n = 3816) [30.4 % vs 11.6 %, OR 4.34, 95 % confidence interval (CI) 1.45-13.03 and 16.7 % vs 11.6 %, OR 2.26, 95 % CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1 %. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95 % CI 0.75-14.96 and OR 3.51, 95 % CI 1.35-9.15 respectively). CONCLUSIONS MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC.
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Affiliation(s)
- Rieko Okada
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan.
| | - Mariko Naito
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Yuta Hattori
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Toshio Seiki
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Hinako Nanri
- Department of Public Health, Showa University School of Medicine, Tokyo, Japan
| | - Miki Watanabe
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.,Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tara Sefanya Kairupan
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Naoyuki Takashima
- Department of Health Science, Shiga University of Medical Science, Otsu, Japan
| | - Haruo Mikami
- Division of Cancer Prevention and Epidemiology, Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Keizo Ohnaka
- Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshiyuki Watanabe
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Sakurako Katsuura-Kamano
- Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Michiaki Kubo
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Nobuyuki Hamajima
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideo Tanaka
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.,Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Chen J, Ying X, Zhang L, Xiang X, Xiong J. Influence of TS and ABCB1 gene polymorphisms on survival outcomes of 5‑FU-based chemotherapy in a Chinese population of advanced gastric cancer patients. Wien Klin Wochenschr 2017; 129:420-426. [DOI: 10.1007/s00508-016-1147-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 11/28/2016] [Indexed: 12/27/2022]
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Richman DM, Tirumani SH, Hornick JL, Fuchs CS, Howard S, Krajewski K, Ramaiya N, Rosenthal M. Beyond gastric adenocarcinoma: Multimodality assessment of common and uncommon gastric neoplasms. Abdom Radiol (NY) 2017; 42:124-140. [PMID: 27645897 DOI: 10.1007/s00261-016-0901-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Despite advances in molecular biology, imaging, and treatment, gastric neoplasms remain a significant cause of morbidity and mortality; gastric adenocarcinoma is the fifth most common malignancy and third most common cause of death worldwide (Brenner et al., Methods Mol Biol 472:467-477, 2009; Howson et al. Epidemiol Rev 8:1-27, 1986; Roder, Gastric Cancer 5(Suppl 1):5-11, 2002; Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. International Agency for Research on Cancer, 2013). Because of both the frequency at which malignant gastric tumors occur as well as the worldwide impact, gastric neoplasms remain important lesions to identify and characterize on all imaging modalities. Despite the varied histologies and behaviors of these neoplasms, many have similar imaging features. Nonetheless, the treatment, management, and prognosis of gastric neoplasms vary by pathology, so it is essential for the radiologist to make every effort to differentiate between these lesions and raise the less common entities as differential diagnostic considerations when appropriate.
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49
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Oh S, Kim N, Kwon JW, Shin CM, Choi YJ, Lee DH, Jung HC. Effect of Helicobacter pylori Eradication and ABO Genotype on Gastric Cancer Development. Helicobacter 2016; 21:596-605. [PMID: 27191536 DOI: 10.1111/hel.12317] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Evidence is lacking regarding how Helicobacter pylori infection status, eradication history, and ABO blood type affect the development of gastric cancer (GC) given the multifactorial and distinctive etiology according to cancer location (noncardia vs cardia) and histologic type (intestinal vs diffuse-type). We evaluated the effect of H. pylori infection status incorporated with H. pylori eradication history and ABO genotype on GC development according to cancer location and histologic type. METHODS A case-control study of 997 patients with noncardia GC (NCGC) and 1147 control subjects was performed using risk analyses with 14 factors including H. pylori infection with eradication history and ABO genotype. As final analyses, multivariable logistic regression models were fitted. Additionally, H. pylori infection status with eradication history was tested for its association with age, atrophic gastritis (AG), and intestinal metaplasia (IM). RESULTS The ABO genotype with the B allele was associated with a significantly lower risk of NCGC of both histologic types. The reduction in risk for NCGC by adding the B allele was more prominent in diffuse-type than that in the intestinal-type. H. pylori infection with eradication history was associated with a significantly lower risk of NCGC of both histologic types, compared with those without eradication history (odds ratio (OR), 0.22; 95% confidence interval (CI), 0.14-0.34) approaching that of uninfected subjects. Past infection status without an eradication history was associated with older age, AG, and IM. CONCLUSIONS H. pylori eradication and the B allele decreased the risks of the intestinal and diffuse-types of NCGC. H. pylori eradication revealed a strong association against developing NCGC. Therefore, it should be considered as a primary measure in NCGC prevention.
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Affiliation(s)
- Sooyeon Oh
- Department of Internal Medicine and Liver Research Institute, Seoul National University, College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University, College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin-Won Kwon
- College of Pharmacy and Research, Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University, College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University, College of Medicine, Seoul, Korea
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50
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Xin J, Song X. Role of peptidylarginine deiminase type 4 in gastric cancer. Exp Ther Med 2016; 12:3155-3160. [PMID: 27882131 PMCID: PMC5103760 DOI: 10.3892/etm.2016.3798] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 08/01/2016] [Indexed: 12/20/2022] Open
Abstract
Peptidylarginine deiminase type 4 (PADI4) post-translationally converts peptidylarginine to citrulline, appearing to be overexpressed in numerous carcinomas. The current study aimed to investigate the expression of PADI4 in gastric cancer tissues and its effect on the biological activities of SGC-7901 and AGS tumor cell lines. The expression of PADI4 was determined in gastric cancer and normal gastric mucosa tissues using western blot analysis and reverse transcription-quantitative polymerase chain reaction. Gastric cancer cell lines were divided into the following groups: Mock group (subjected to transfection reagent); negative group [subjected to small interfering RNA (siRNA) transfection]; PADI4 siRNA group (subjected to PADI4 siRNA transfection); 5-fluorouracil (5-Fu) group (subjected to 5-Fu); and 5-Fu + siRNA transfection group (subjected to 5-Fu and PADI4 siRNA transfection). The effects of silencing PADI4 with the above measures on the proliferation and invasion of SGC-7901 and AGS cells were determined by MTT and Transwell chamber assays. In addition, propidium iodide staining was performed to detect the effects of PADI4 on the cell cycle. A significant increase in the expression of PADI4 mRNA in gastric cancer tissue compared with normal mucosa tissue was identified (P<0.05). The proliferation and invasion of SGC-7901 and AGS cells were significantly decreased in the PADI4 siRNA group. Furthermore, flow cytometry DNA analysis revealed that silencing PADI4 resulted in significant S phase arrest and marked decrease of cells in the G2/M phase. PADI4 siRNA coupled with 5-Fu significantly enhanced its inhibitory effect on the proliferation of gastric cancer cells. In conclusion, PADI4 demonstrated high expression in gastric cancer and served an important role in the biological activities of gastric cancer cells involving cell proliferation, invasion and cell cycle. As a result, PADI4 may be a valid cancer susceptibility gene and potential target for cancer therapy.
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Affiliation(s)
- Jiang Xin
- Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China; Department of General Surgery, The Third People's Hospital of Qingdao, Qingdao, Shandong 266004, P.R. China
| | - Xiuqi Song
- Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China; Department of General Surgery, Qingdao Central Hospital, Qingdao, Shandong 266402, P.R. China
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