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Jiang YK, Li W, Qiu YY, Yue M. Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer. World J Gastrointest Oncol 2024; 16:2318-2334. [PMID: 38994153 PMCID: PMC11236256 DOI: 10.4251/wjgo.v16.i6.2318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 04/04/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024] Open
Abstract
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.
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Affiliation(s)
- Ya-Kun Jiang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Wei Li
- Health Management Center, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Ying-Yang Qiu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Meng Yue
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
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Tian Y, Xie Y, Yi G, Wu F, Dang X, Bai F, Wang J, Zhang D. Prognostic Value and Therapeutic Significance of CCL Chemokines in Gastric Cancer. Curr Med Chem 2024; 31:7043-7058. [PMID: 39129286 DOI: 10.2174/0109298673315146240731100101] [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: 03/07/2024] [Revised: 06/10/2024] [Accepted: 07/02/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health. AIMS CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines. METHODS In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer. RESULTS The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration. CONCLUSION These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.
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Affiliation(s)
- Yonggang Tian
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
| | - Yunqian Xie
- Department of Gastroenterology, The Gastroenterology Clinical Medical Center of Hainan Province, The Second Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China
| | - Guirong Yi
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
| | - Fanqi Wu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China
| | - Xiaoyu Dang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China
| | - Feihu Bai
- Department of Gastroenterology, The Gastroenterology Clinical Medical Center of Hainan Province, The Second Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China
| | - Jun Wang
- Department of Gastroenterology, 986 Hospital, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi Province, China
| | - Dekui Zhang
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
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Chen L, Yang X, Yang X, Fan K, Xiao P, Zhang J, Wang X. Association between the expression levels of tumor necrosis factor-α-induced protein 8 and the prognosis of patients with gastric adenocarcinoma. Exp Ther Med 2016; 12:238-244. [PMID: 27347043 PMCID: PMC4906960 DOI: 10.3892/etm.2016.3327] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 03/17/2016] [Indexed: 12/11/2022] Open
Abstract
The present study aimed to investigate the expression levels of tumor necrosis factor-α-induced protein 8 (TNFAIP8) in gastric adenocarcinoma. TNFAIP8 expression levels in gastric adenocarcinoma tissue samples (with and without lymph node metastasis), adjacent normal tissue samples and metastatic lymph node tissue samples were detected by immunohistochemistry. The correlation between TNFAIP8 expression levels and clinicopathological data and gastric adenocarcinoma prognosis was analyzed. The results demonstrated that TNFAIP8 expression in gastric adenocarcinoma tissue samples and metastatic lymph node tissue samples markedly increased at a rate of 47.2% (50/106) and 81.7% (49/60), respectively, as compared with the adjacent normal tissue samples in which no TNGFAIP8 expression was detected (0%). This increase in TNFAIP8 expression was statistically significant. TNFAIP8 expression rates in the primary tumors (60%, 36/60) of patients with lymph node metastasis were significantly higher compared with the primary tumors of patients without lymph node metastasis (30.4%, 14/46). TNFAIP8 expression was associated with an increase in the severity of TNM stage, tumor grade, vascular invasion, lymph node metastasis and serum CA72-4 levels. The overall survival rate of patients with gastric adenocarcinoma and high TNFAIP8 expression was poorer compared with patients with low TNFAIP8 expression, and TNFAIP8 expression was negatively correlated with patient prognosis. The results also demonstrated that TNFAIP8 was an independent prognostic marker in gastric adenocarcinoma (relative risk, 1.736; P=0.029). In conclusion, the results of the present study demonstrated that TNFAIP8 expression was associated with the occurrence, development and metastasis of gastric adenocarcinoma, and negatively correlated with the prognosis of patients with gastric adenocarcinoma. TNFAIP8 may therefore serve as a prognostic factor for gastric adenocarcinoma.
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Affiliation(s)
- Ling Chen
- Department of Medical Oncology, Cancer Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Department of Internal Medicine-Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
| | - Xigui Yang
- Department of Internal Medicine-Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
| | - Xiangshan Yang
- Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
| | - Kaixi Fan
- Department of Internal Medicine-Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
| | - Ping Xiao
- Department of Internal Medicine-Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
| | - Jing Zhang
- Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
| | - Xiuwen Wang
- Department of Medical Oncology, Cancer Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
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Urbanska AM, Karagiannis ED, Au AS, Dai SY, Mozafari M, Prakash S. What's Next for Gastrointestinal Disorders: No Needles? J Control Release 2016; 221:48-61. [PMID: 26646543 DOI: 10.1016/j.jconrel.2015.11.031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 11/26/2015] [Accepted: 11/27/2015] [Indexed: 12/28/2022]
Abstract
A myriad of pathologies affect the gastrointestinal tract, citing this affected area as a significant target for therapeutic intervention. One group of therapeutic agents, antisense and oligonucleotides and small interfering RNAs, offer a promising platform for treating a wide variety of diseases ranging from cancer to auto-immune diseases. Current delivery methods are carried out either systemically or locally into diseased areas, both of which involve needles. The challenge in orally administering this type of treatment lies in the complications that arise due to the vast environmental extremes found within the gastrointestinal tract, owing to the fact that, as the drug travels down the gastrointestinal tract, it is subjected to pH changes and interactions with bacteria and a variety of digestive and protective enzymes including proteases, DNAses, and RNAses. Overcoming these challenges to allow the practical application of these drugs is a priority that has invoked a multitude of research in the chemical, biological, and material sciences. In this review, we will address common gastrointestinal pathologies, the barriers to oral-based therapies and antisense-interfering technologies, the approaches that have already been applied for their delivery, and the current status of antisense drug therapy clinical trials for gastrointestinal-related disorders.
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Affiliation(s)
- Aleksandra M Urbanska
- Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, Canada
| | - Emmanouil D Karagiannis
- Synthetic Neurobiology Group, Massachusetts Institute of Technology Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Cambridge, MA 02139, USA
| | - Andrew S Au
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY 10032-3802, USA
| | - Si Yuan Dai
- Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, Canada
| | - Masoud Mozafari
- Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran.
| | - Satya Prakash
- Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3775 University Street, Montreal, Quebec, Canada
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Yin XF, Chen J, Mao W, Wang YH, Chen MH. A selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits gastric cancer cell growth. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2012; 31:46. [PMID: 22592002 PMCID: PMC3403951 DOI: 10.1186/1756-9966-31-46] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 05/16/2012] [Indexed: 12/20/2022]
Abstract
Background Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor associated with gastric carcinogenesis. 3,3'-Diindolylmethane (DIM) is a relatively non-toxic selective AhR modulator. This study was to detect the effects of DIM on gastric cancer cell growth. Methods Gastric cancer cell SGC7901 was treated with DIM at different concentrations (0,10,20,30,40,50 μmol/L) with or without an AhR antagonist, resveratrol. The expression of AhR and Cytochrome P4501A1 (CYP1A1), a classic target gene of AhR pathway, were detected by RT-PCR and Western blot; cell viability was measured by MTT assay, and the changes in cell cycle and apoptosis were analyzed by flow cytometry. Results RT-PCR and western-blot showed that with the increase of the concentration of DIM, AhR protein gradually decreased and CYP1A1 expression increased, suggesting that DIM activated the AhR pathway and caused the translocation of AhR from cytoplasm to nucleus. MTT assay indicated that the viability of SGC7901 cells was significantly decreased in a concentration- and time-dependent manner after DIM treatment and this could be partially reversed by resveratrol. Flow cytometry analysis showed that DIM arrested cell cycle in G1 phase and induced cell apoptosis. Conclusion Selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. AhR may be a potential therapeutic target for gastric cancer treatment.
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Affiliation(s)
- Xiao-Fei Yin
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China
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Gong Y, Guo MZ, Ye ZJ, Zhang XL, Zhao YL, Yang YS. Silence of HIN-1 expression through methylation of its gene promoter in gastric cancer. World J Gastroenterol 2011; 17:526-33. [PMID: 21274384 PMCID: PMC3027021 DOI: 10.3748/wjg.v17.i4.526] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Revised: 11/02/2010] [Accepted: 11/09/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development.
METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2’-deoxycytidine treatment.
RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2’-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000).
CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.
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Hu H, Zhang Y, Zou M, Yang S, Liang XQ. Expression of TRF1, TRF2, TIN2, TERT, KU70, and BRCA1 proteins is associated with telomere shortening and may contribute to multistage carcinogenesis of gastric cancer. J Cancer Res Clin Oncol 2010; 136:1407-14. [PMID: 20127252 DOI: 10.1007/s00432-010-0795-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2009] [Accepted: 01/14/2010] [Indexed: 12/17/2022]
Abstract
PURPOSE Telomere dysfunction is believed to be a significant factor in carcinogenesis. To elucidate the carcinogenesis mechanism in gastric cancer, the expression of telomeric proteins and changes in telomere length were investigated during multistage carcinogenesis of gastric cancer. METHODS Tissue samples were obtained during surgical operations from the normal gastric mucosa of 10 patients, the precancerous lesions of 15 patients, the gastric cancer tissues (GC) of 20 patients, and of tumors due to gastric cancer with lymph node metastasis (GCLM) from 5 patients. The expression of TRF1, TRF2, and TIN2 proteins was measured by Western blotting, while the expression of TERT, KU70, and BRCA1 proteins was detected using the immunohistochemical method. The mean telomere length was determined by Southern blotting. RESULTS Compared with normal gastric mucosa tissues, the expression of TRF1, TRF2, and TIN2 proteins was significantly higher in precancerous lesions, GC, and GCLM (P < 0.01). The expression of TRF1, TRF2, and TIN2 proteins was significantly higher in GC and GCLM than in precancerous lesions (P < 0.01). The expression of TERT and Ku70 proteins in precancerous lesions and GC tissues was significantly higher than that in normal gastric mucosa tissues (P < 0.01). The expression of TERT and Ku70 proteins in GC tissues was significantly higher than in precancerous lesions (P < 0.01). In normal gastric mucosa, the BRCA1 protein was primarily located in the cell nucleus. In precancerous lesions and GC, the expression of the BRCA1 protein was apparent in the cell cytoplasm. The mean telomere length in precancerous lesions, GC, and GCLM was significantly shorter than that in normal gastric mucosa tissues (P < 0.05). The mean telomere length in GC and GCLM was significantly shorter than that in precancerous lesions (P < 0.05). The mean telomere length in all tissue samples was inversely correlated with the level of TRF1, TRF2, TIN2, TERT, and Ku70 proteins. CONCLUSIONS Our results suggest that the over-expression of telomeric proteins, TRF1, TRF2, TIN2, TERT, and Ku70, and the transposition of the BRCA1 protein may work together to reduce the telomere length in precancerous lesions and gastric cancer, and could contribute to the multistage carcinogenesis of gastric cancer. These findings offer new insight into the mechanism of carcinogenesis in gastric cancer.
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Affiliation(s)
- Hua Hu
- Cancer Research Institute, The Second Affiliated Hospital, University of South China, 421001, Hengyang, Hunan, People's Republic of China
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Peng TL, Chen J, Mao W, Liu X, Tao Y, Chen LZ, Chen MH. Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer. World J Gastroenterol 2009; 15:1719-29. [PMID: 19360915 PMCID: PMC2668777 DOI: 10.3748/wjg.15.1719] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the functional significance of aryl hydrocarbon receptor (AhR) in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC) treatment.
METHODS: RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.
RESULTS: AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase.
CONCLUSION: AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.
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Burgermeister E, Xing X, Röcken C, Juhasz M, Chen J, Hiber M, Mair K, Shatz M, Liscovitch M, Schmid RM, Ebert MPA. Differential expression and function of caveolin-1 in human gastric cancer progression. Cancer Res 2007; 67:8519-26. [PMID: 17875691 DOI: 10.1158/0008-5472.can-07-1125] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Caveolin-1 is a scaffold protein of caveolae that acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. The role of caveolin-1 in the pathogenesis of gastric cancer (GC) is currently unknown. We show by confocal immunofluorescence microscopy and immunohistochemistry of biopsies from GC patients (n = 41) that the nonneoplastic mucosa expressed caveolin-1 in foveolar epithelial cells and adjacent connective tissue. GC cells of only 3 of 41 (7%) patients expressed caveolin-1 and were all of the intestinal type. Quantitative PCR and Western blotting confirmed that, compared with nonneoplastic tissue, the overall caveolin-1 mRNA was decreased in 14 of 19 (74%) GC patients and protein in 7 of 13 (54%), respectively. Strong caveolin-1 reactivity was found in the nonepithelial compartment (myocytes, fibroblasts, perineural, and endothelial cells) in both tumor-free and GC samples. In a series of human GC cell lines, caveolin-1 expression was low in cells derived from a primary tumor (AGS and SNU-1) but was increased in cell lines originating from distant metastases (MKN-7, MKN-45, NCI-N87, KATO-III, and SNU-5). Ectopic expression of caveolin-1 in AGS cells decreased proliferation but promoted anchorage-independent growth and survival. RNAi-mediated knockdown of endogenous caveolin-1 in MKN-45 cells accelerated cell growth. These data indicate that caveolin-1 exhibits a stage-dependent differential expression and function in GC and may thereby contribute to its pathogenesis.
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Affiliation(s)
- Elke Burgermeister
- Department of Medicine II, Klinikum rechts der Isar, Technical University of München, Munich, Germany
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Abstract
AIM: To investigate the expression and localization of periostin in gastric cancer and its clinical relevance.
METHODS: Reverse transcriptase polymerase chain reaction was used to measure periostin mRNA expression. Western blotting was carried out to detect periostin protein expression. Immunohistochemistry was performed to localize and quantify the expression of periostin in benign gastric diseases and gastric cancer, and immunostaining results were correlated with gastric cancer pathological stages.
RESULTS: Periostin expression was low at both mRNA and protein levels in normal gastric tissues, but was overexpressed in gastric cancer tissues. Immunohistochemical staining revealed that periostin was overexpressed in primary gastric cancer, as well as in metastatic lymph nodes, but only faint staining was found in benign gastric ulcers. By quantitative analysis of the immunostaining results, periostin expression was increased 2.5-4-fold in gastric cancer, compared to that in benign gastric disease, and there was a trend toward increasing periostin expression with tumor stage.
CONCLUSION: This observation demonstrated that periostin was overexpressed in gastric cancer and lymph node metastasis, which suggests that periostin plays an important role in the progression and metastasis of gastric cancer.
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Affiliation(s)
- Jun-Sheng Li
- Department of General Surgery, Affiliated Zhong-Da Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China.
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Wiwanitkit V. Cancer immunomics and application of 'omics' for cancer management. Expert Rev Clin Immunol 2007; 3:807-12. [PMID: 20477030 DOI: 10.1586/1744666x.3.5.807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Several 'omics' sciences have been launched. The outstanding diversity of immune system components, together with the complexity of the regulatory pathways and network-type interactions, makes immunology a combinatorial science. Cancer immonomics is a branch of immunomics. The present cancer immunomics project aims at diagnostics and therapy. Comparative and structural genomics can be applied for understanding the underlying tumorogenesis process. For diagnostic purposes, in order to develop a new marker, gene expression analysis technologies, such as DNA microarray, differential display, cDNA subtraction, serial analysis of gene expression and serological proteome analysis, which enable investigators to obtain comprehensive data with respect to gene expression profiles, are progressing rapidly. For therapeutic purposes, vaccine candidate finding, gene therapy and drug-tumor interaction modeling can be clarified by the advance immunomics techniques. In this article, the author will present the basic concepts on cancer immunomics and application for basic study of the pathogenesis, diagnosis and treatment of cancer.
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Affiliation(s)
- Viroj Wiwanitkit
- Wiwanitkit House, 38/167 Soi Yim Prayoon Sukhapiban 1 Road Bangkhae, Bangkok 10160, Thailand.
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Chen CD, Wang CS, Huang YH, Chien KY, Liang Y, Chen WJ, Lin KH. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance. Proteomics 2007; 7:155-67. [PMID: 17154271 DOI: 10.1002/pmic.200600663] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Gastric cancer is the second most common cancer worldwide and the fifth leading cause of cancer-related death in Taiwan. Identification of biomarkers is essential to improve patient survival. Fifty aberrantly expressed proteins were identified using 2-DE combined with MALDI TOF MS and were grouped based on their function. The overexpression of proteins was confirmed using real-time quantitative RT-PCR, Western blot, and immunohistochemical analysis. The clinicopathological correlations and prognostic significance of these aberrantly expressed proteins were evaluated to determine the novel gastric cancer biomarkers. In this study, expression of chloride intracellular channel 1 (CLIC1) is significantly up-regulated in 67.9% of gastric patients and was selected for further study. The CLIC1 expression in tumor tissues was increased by 1.95-fold (range, 0.01-6.19-fold) compared with that expressed by adjacent noncancerous mucosa. Elevated CLIC1 expression was strongly correlated with lymph node metastasis, lymphatic invasion, perineural invasion, and pathological staging. Additionally, the 5-year survival rate for the low CLIC1 expression group (n = 28; <1.72-fold) was higher than that for the high CLIC1 expression group (n = 28; >or=1.72-fold) (log rank, p = 0.0300). Experimental results indicate that overexpression of CLIC1 is a potential prognostic marker for gastric cancer.
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Affiliation(s)
- Chi-De Chen
- Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan, Republic of China
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13
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Ebert MPA, Niemeyer D, Deininger SO, Wex T, Knippig C, Hoffmann J, Sauer J, Albrecht W, Malfertheiner P, Röcken C. Identification and confirmation of increased fibrinopeptide a serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry. J Proteome Res 2006; 5:2152-8. [PMID: 16944926 DOI: 10.1021/pr060011c] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Gastric cancer is the second most common malignancy and prognosis remains dismal. The reasons for the poor prognosis are the lack of sensitive serum markers for early detection and screening of high-risk individuals as well as the limited treatment options in advanced cancer stages. Using MALDI-TOF mass spectrometry after prefractionation of sera with magnet hydrophobic C8 coated beads sera from 14 patients with gastric cancer and 14 healthy controls mass spectra were generated. A peptide fragment was found to be highly elevated in cancer sera and was identified as fibrinopeptide A. To confirm proteome analysis of gastric cancer sera, we then screened a larger series of patients with gastric cancer (n = 99), high-risk individuals (n = 13) and normal controls (n = 111) for fibrinopeptide A serum levels. Interestingly, the mean logarithmic concentrations of serum fibrinopeptide A levels were significantly higher in cancer patients (mean 3.636 +/- 0.3738; p < 0.0001) and high-risk individuals (mean 3.569 +/- 0.4722; p < 0.05) compared to normal controls (mean 3.303 +/- 0.4012). In contrast, we observed no association of fibrinopeptide A levels with tumor stage, tumor location, presence of regional or distant metastasis, and Lauren type of gastric cancer. In conclusion, MALDI-TOF mass spectrometry of prefractionated gastric cancer sera allows the identification of potential biomarkers that may lead to the development of serum based tests for screening of high-risk individuals.
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Affiliation(s)
- Matthias P A Ebert
- Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, München, Germany.
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Clark CJ, Thirlby RC, Picozzi V, Schembre DB, Cummings FP, Lin E. Current problems in surgery: gastric cancer. Curr Probl Surg 2006; 43:566-670. [PMID: 17000267 DOI: 10.1067/j.cpsurg.2006.06.003] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Clancy J Clark
- Department of General Surgery, Virginia Mason Medical Center, Seattle, Washington, USA
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Wang X, Zhu W, Pradhan K, Ji C, Ma Y, Semmes OJ, Glimm J, Mitchell J. Feature extraction in the analysis of proteomic mass spectra. Proteomics 2006; 6:2095-100. [PMID: 16502467 DOI: 10.1002/pmic.200500459] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Feature extraction or biomarker selection is a critical step in disease diagnosis and knowledge discovery based on protein MS. Many studies have discussed the classification methods applied in proteomics; however, few could be found to address feature extraction in detail. In this paper, we developed a systematic approach for the extraction of mass spectrum peak apex and peak area with special emphasis on noise filtration and peak calibration. Application to a head and neck cancer data generated at the Eastern Virginia Medical School [Wadsworth, J. T., Somers, K. D., Cazares, L. H., Malik, G. et al.., Clin. Cancer Res. 2004, 10, 1625-1632] revealed that the new feature extraction method would yield consistent and highly discriminatory biomarkers.
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Affiliation(s)
- Xuena Wang
- State University of New York, Stony Brook, NY, USA
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16
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Di Mario F, Cavallaro LG, Cavestro GM, Franzé A. Are there useful biomarkers for gastric cancer? Dig Liver Dis 2006; 38:308-309. [PMID: 16522379 DOI: 10.1016/j.dld.2006.01.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2006] [Accepted: 01/12/2006] [Indexed: 12/11/2022]
Affiliation(s)
- F Di Mario
- Department of Clinical Sciences, Section of Gastroenterology, University of Parma, 43100 Parma, Italy.
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