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Li JH, Zhang DY, Zhu JM, Dong L. Clinical applications and perspectives of circulating tumor DNA in gastric cancer. Cancer Cell Int 2024; 24:13. [PMID: 38184573 PMCID: PMC10770949 DOI: 10.1186/s12935-024-03209-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 01/02/2024] [Indexed: 01/08/2024] Open
Abstract
Gastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the blood. Numerous gastric cancer-specific ctDNA biomarkers have now been identified. CtDNA analysis provides insight into genetic and epigenetic alterations in tumors, holding promise for predicting treatment response and prognosis in gastric cancer patients. This review summarizes current research on ctDNA biology and detection technologies, while highlighting clinical applications of ctDNA for gastric cancer diagnosis, prognosis, and guiding treatment decisions. Current challenges and future perspectives for ctDNA analysis are also discussed.
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Affiliation(s)
- Jing-Han Li
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Dan-Ying Zhang
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Ji-Min Zhu
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Ling Dong
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
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Huang ZB, Zhang HT, Yu B, Yu DH. Cell-free DNA as a liquid biopsy for early detection of gastric cancer. Oncol Lett 2021; 21:3. [PMID: 33240409 PMCID: PMC7681206 DOI: 10.3892/ol.2020.12264] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis worldwide, mainly due to the lack of suitable modalities for population-based screening and early detection of this disease. Therefore, novel and less invasive tests with improved clinical utility are urgently required. The remarkable advances in genomics and proteomics, along with emerging new technologies for highly sensitive detection of genetic alterations, have shown the potential to map the genomic makeup of a tumor in liquid biopsies, in order to assist with early detection and clinical management. The present review summarize the current status in the identification and development of cell-free DNA (cfDNA)-based biomarkers in GC, and also discusses their potential utility and the technical challenges in developing practical cfDNA-based liquid biopsy for early detection of GC.
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Affiliation(s)
- Zheng-Bin Huang
- Department of Surgery, Hanchuan Renmin Hospital, Hanchuan, Hubei 431600, P.R. China
| | - Hai-Tao Zhang
- Department of Gastrointestinal Surgery, The Second People's Hospital of Shenzhen, Shenzhen, Guangdong 518037, P.R. China
| | - Benjamin Yu
- Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - De-Hua Yu
- Shenzhen USK Bioscience Co., Ltd., Shenzhen, Guangdong 518110, P.R. China
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S-1 combined with paclitaxel may benefit advanced gastric cancer: Evidence from a systematic review and meta-analysis. Int J Surg 2019; 62:34-43. [PMID: 30641155 DOI: 10.1016/j.ijsu.2018.11.010] [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: 07/17/2018] [Revised: 10/13/2018] [Accepted: 11/07/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Gastric cancer, as one of the increasingly common malignancies, has experienced high morbidity throughout many countries at present. Currently, chemotherapy regimen with more efficacy and safety for advanced gastric cancer (AGC) is needed. We aimed to assess the clinical efficacy and safety of S-1 combined with paclitaxel (PTX) for AGC by performing a systematic review and meta-analysis of the published studies. METHOD All published randomized controlled trials (RCTs) of S-1 combined with PTX for AGC were searched. Studies that included patients with locally advanced or metastases' gastric cancers were included. We searched the databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, American Society of Clinical Oncology meeting abstracts and China National Knowledge Internet (CNKI) from 2000 to 2018. We searched the database up to January 2018. The first endpoint was overall survival (OS). Other endpoints were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Safety analyses were also performed. RESULTS A total of 7 trials (including 1407 patients, 711 patients in intervention group and 696 patients in control group) were included in the present analysis. S-1 combined with PTX significantly improved the OS [HR = 0.78, 95% CI: 0.60-0.97, P = 0.000],PFS [HR = 0.70, 95% CI: 0.55-0.85, P = 0.000], ORR [RR = 1.30, 95%CI: 1.05-1.60, P = 0.017] and DCR [RR = 1.15, 95%CI: 1.04-1.27, P = 0.008] of patients with AGC. The grade 3 or 4 haematological and non-hematologic toxicities were anemia [RR = 1.71, 95% CI: 1.04-2.79, P = 0.03], neutropenia [RR = 1.65, 95% CI: 1.32-2.06, P < 0.0001] and anorexia [RR = 1.66, 95% CI: 1.05-2.64, P = 0.03] respectively. CONCLUSION S-1 combined with PTX may be a good choice for patients with AGC. S-1 plus PTX experienced more efficacy and safety when compared with S-1 alone or S-1 plus other drugs.
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Normando SRC, Delgado PDO, Rodrigues AKSB, David Filho WJ, Fonseca FLA, Cruz FJSM, del Giglio A. Circulating free plasma tumor DNA in patients with advanced gastric cancer receiving systemic chemotherapy. BMC Clin Pathol 2018; 18:12. [PMID: 30498396 PMCID: PMC6258437 DOI: 10.1186/s12907-018-0079-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 11/13/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Advanced gastric cancers are usually associated with incurable conditions for which systemic treatments are indicated. Recent studies suggest that circulating cell-free plasma DNA of tumour origin (tDNA) is a promising non-invasive biomarker that can be used to predict the prognosis and monitor the efficacy of systemic treatments in patients with certain types of cancer. We conducted a pilot study to analyse the potential role of tDNA as a biomarker in patients with advanced gastric cancer. METHODS We included 30 patients with locally advanced unresectable or metastatic gastric cancer. We obtained samples (10 mL of total blood) from each patient every 3 months and performed concomitant CT until disease progression or death. Total cell-free circulating DNA (cfDNA) samples were measured using GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd. The cfDNA was used to evaluate the ALU DNA sequences 247 and 115. The level of tDNA was calculated from the ratio of the expression of ALU DNA sequences and the concentration of total cell-free DNA. We utilized the RECIST criteria 1.1 to evaluate the tumour response. RESULTS Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls (p = 0.00015), which allowed us to conclude that the cfDNA in the patients originated from the tumour. We did not find any significant correlation between the level of tDNA and OS or tumour response. However, after the first cycles of chemotherapy (at 3 months), we observed that patients with lower tDNA levels had significantly longer DFS compared with those with higher levels (Cox Regression p = 0.0228). CONCLUSIONS At 3 months after the beginning of chemotherapy, the tDNA levels are correlated with DFS in patients with advanced gastric cancer who receive systemic chemotherapy. tDNA may be a specific, non-invasive and cost effective new biomarker for these patients.
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Affiliation(s)
| | | | | | | | | | - Felipe José Silva Melo Cruz
- Discipline of Hematology and Oncology at ABC Foundation School of Medicine, Santo André, Brazil
- Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, Brazil
| | - Auro del Giglio
- Discipline of Hematology and Oncology at ABC Foundation School of Medicine, Santo André, Brazil
- Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, Brazil
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Song M, Camargo MC, Weinstein SJ, Best AF, Männistö S, Albanes D, Rabkin CS. Family history of cancer in first-degree relatives and risk of gastric cancer and its precursors in a Western population. Gastric Cancer 2018; 21:729-737. [PMID: 29455268 PMCID: PMC7380686 DOI: 10.1007/s10120-018-0807-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 02/07/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Family history may inform risks of gastric cancer and preneoplastic lesions. METHODS We examined associations with history of cancer in first-degree relatives for 307 incident gastric cancer cases among 20,720 male smokers in a prospective study in Finland. Cox regression was used to calculate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI). Logistic regression was used to estimate odds ratios (OR) and 95% CIs for low serum pepsinogen, a marker of gastric atrophy. RESULTS Gastric cancer risk was associated with gastric cancer history in first-degree relatives overall (HR 1.56, 95% CI 1.15-2.12), in fathers (HR 1.67, 95% CI 1.09-2.55) and in siblings (HR 2.05, 95% CI 1.25-3.38). Associations were significant for noncardia (HR 1.83, 95% CI 1.30-2.57) but not cardia (HR 0.93, 95% CI 0.46-1.87) cancers, and marginal for both intestinal-(HR 1.53, 95% CI 0.92-2.55) and diffuse-type (HR 1.47, 95% CI 0.72-3.03) histologies. Family history of other cancer types was not associated with gastric cancer risk. Family history of gastric cancer was associated with low pepsinogen (OR 1.29, 95% CI 1.11-1.50). CONCLUSIONS Family history of gastric cancer is strongly associated with specific subtypes of gastric cancer as well as with gastric atrophy, a risk factor for developing this malignancy.
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Affiliation(s)
- Minkyo Song
- Division of Cancer Epidemiology and Genetics, Department of
Health and Human Services, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA;,Correspondence to: Name: Minkyo Song,
Address: Infections and Immunoepidemiology Branch, Division of Cancer
Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive,
6E204, Bethesda, MD 20892-9776, Phone: 240-276-7985, Fax: 240-276-7806,
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, Department of
Health and Human Services, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA
| | - Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, Department of
Health and Human Services, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA
| | - Ana F. Best
- Division of Cancer Epidemiology and Genetics, Department of
Health and Human Services, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA
| | - Satu Männistö
- Department of Public Health Solutions, National Institute
for Health and Welfare, Helsinki, Finland
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, Department of
Health and Human Services, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA
| | - Charles S. Rabkin
- Division of Cancer Epidemiology and Genetics, Department of
Health and Human Services, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA
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Traditional Chinese medicine integrated with chemotherapy for stage IV non-surgical gastric cancer: a retrospective clinical analysis. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2018; 15:469-475. [PMID: 29103417 DOI: 10.1016/s2095-4964(17)60377-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Traditional Chinese medicine (TCM) is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status (KPS) score were measured as the main outcome. RESULTS The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups (χ2 = 42.244, P > 0.001). After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively (P > 0.001). The Cox regression analysis showed that TCM treatment is a protective factor for patients' overall survival. CONCLUSION This study demonstrated that TCM integrated with chemotherapy may prolong overall survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer.
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Liu S, Zhu Y, Lin LW, Ding SK, Lin XC, Zhong KL, Pan K, Dai Y. The composition and variation of the BCR CDR3s in gastric cancer. Oncol Lett 2018; 16:239-246. [PMID: 29928407 PMCID: PMC6006485 DOI: 10.3892/ol.2018.8677] [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: 11/21/2017] [Accepted: 04/26/2018] [Indexed: 12/25/2022] Open
Abstract
Gastric cancer (GC) is the fourth most common type of cancer and the second most common cause of cancer-associated mortality worldwide. B cell-associated autoantibodies against tumor-associated antigens are attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer. This is due to their specificity and stability in the sera. In the present study multiplex polymerase chain reaction and Illumina high-throughput sequencing (HTS) was used to study the composition and variation of the B cell receptor (BCR) complimentary-determining region 3 (CDR3) in GC. The peripheral blood, cancer tissues and peri-cancer tissues were included from 7 patients with GC. On average there was a total of 403,959 CDR3 sequences, with 72,367 unique CDR3 nt sequences and 61,709 unique CDR3 aa sequences per sample identified, which are critical for further understanding the BCR repertoire in GC. The details of GC CDR3s may accelerate the screening process for possible new autoantigens and may provide additional information necessary for generating effective B cell targeted diagnosis and therapeutic strategies.
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Affiliation(s)
- Song Liu
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Ying Zhu
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Lie-Wen Lin
- Department of Gastrointestinal Surgery, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Shun-Kai Ding
- Department of Gastrointestinal Surgery, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Xiao-Cong Lin
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Ke-Li Zhong
- Department of Gastrointestinal Surgery, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Kai Pan
- Department of Gastrointestinal Surgery, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Yong Dai
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
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Sahin D, Taflan SO, Yartas G, Ashktorab H, Smoot DT. Screening and Identification of Peptides Specifically Targeted to Gastric Cancer Cells from a Phage Display Peptide Library. Asian Pac J Cancer Prev 2018; 19:927-932. [PMID: 29693344 PMCID: PMC6031796 DOI: 10.22034/apjcp.2018.19.4.927] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Background: Gastric cancer is the second most common cancer among the malign cancer types. Inefficiency of
traditional techniques both in diagnosis and therapy of the disease makes the development of alternative and novel
techniques indispensable. As an alternative to traditional methods, tumor specific targeting small peptides can be used
to increase the efficiency of the treatment and reduce the side effects related to traditional techniques. The aim of this
study is screening and identification of individual peptides specifically targeted to human gastric cancer cells using
a phage-displayed peptide library and designing specific peptide sequences by using experimentally-eluted peptide
sequences. Methods: Here, MKN-45 human gastric cancer cells and HFE-145 human normal gastric epithelial cells
were used as the target and control cells, respectively. 5 rounds of biopannning with a phage display 12-peptide library
were applied following subtraction biopanning with HFE-145 control cells. The selected phage clones were established
by enzyme-linked immunosorbent assay and immunofluorescence detection. We first obtain random phage clones
after five biopanning rounds, determine the binding levels of each individual clone. Then, we analyze the frequencies
of each amino acid in best binding clones to determine positively overexpressed amino acids for designing novel
peptide sequences. Results: DE532 (VETSQYFRGTLS) phage clone was screened positive, showing specific binding
on MKN-45 gastric cancer cells. DE-Obs (HNDLFPSWYHNY) peptide, which was designed by using amino acid
frequencies of experimentally selected peptides in the 5th round of biopanning, showed specific binding in MKN-45
cells. Conclusion: Selection and characterization of individual clones may give us specifically binding peptides, but
more importantly, data extracted from eluted phage clones may be used to design theoretical peptides with better
binding properties than even experimentally selected ones. Both peptides, experimental and designed, may be potential
candidates to be developed as useful diagnostic or therapeutic ligand molecules in gastric cancer research.
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Affiliation(s)
- Deniz Sahin
- Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
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Wang S, Qin J, Ye H, Wang K, Shi J, Ma Y, Duan Y, Song C, Wang X, Dai L, Wang K, Wang P, Zhang J. Using a panel of multiple tumor-associated antigens to enhance autoantibody detection for immunodiagnosis of gastric cancer. Oncoimmunology 2018; 7:e1452582. [PMID: 30221047 PMCID: PMC6136883 DOI: 10.1080/2162402x.2018.1452582] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 03/08/2018] [Accepted: 03/10/2018] [Indexed: 12/27/2022] Open
Abstract
Autoantibodies against tumor-associated antigens (TAAs) are attractive non-invasive biomarkers for detection of cancer due to their inherently stable in serum. Serum autoantibodies against 9 TAAs from gastric cancer (GC) patients and healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). A logistic regression model predicting the risk of being diagnosed with GC in the training cohort (n = 558) was generated and then validated in an independent cohort (n = 372). Area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance. Finally, an optimal prediction model with 6 TAAs (p62, c-Myc, NPM1, 14-3-3ξ, MDM2 and p16) showed a great diagnostic performance of GC with AUC of 0.841 in the training cohort and 0.856 in the validation cohort. The proportion of subjects being correctly defined were 78.49% in the training cohort and 81.99% in the validation cohort. This prediction model could also differentiate early-stage (stage I-II) GC patients from healthy controls with sensitivity/specificity of 76.60%/72.34% and 80.56%/79.17% in the training and validation cohort, respectively, and the overall sensitivity/specificity for early-stage GC were 78.92%/74.70% when being combined with two cohorts. This prediction model presented no significant difference for the diagnostic accuracy between early-stage and late-stage (stage III - IV) GC patients. The model with 6 TAAs showed a high diagnostic performance for GC detection, particularly for early-stage GC. This study further supported the hypothesis that a customized array of multiple TAAs was able to enhance autoantibody detection in the immunodiagnosis of GC.
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Affiliation(s)
- Shuaibing Wang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Jiejie Qin
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Hua Ye
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Keyan Wang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Jianxiang Shi
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Yan Ma
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Yitao Duan
- Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Chunhua Song
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Xiao Wang
- Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Liping Dai
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
- Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Kaijuan Wang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Peng Wang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
| | - Jianying Zhang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China
- Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
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Song M, Camargo MC, Weinstein SJ, Murphy G, Freedman ND, Koshiol J, Stolzenberg-Solomon RZ, Abnet CC, Männistö S, Albanes D, Rabkin CS. Serum pepsinogen 1 and anti-Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males. Aliment Pharmacol Ther 2018; 47:494-503. [PMID: 29243850 PMCID: PMC5776724 DOI: 10.1111/apt.14471] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 10/29/2017] [Accepted: 11/23/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori serology have been used for gastric risk stratification in Asia. AIM To assess utility of these markers in a Western population. METHODS SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 μg/L). In a subset (n = 3555) with anti-H. pylori serology, these markers jointly defined the following: Group A (H. pylori[-], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[-], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression. RESULTS There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre-diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99-3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21-2.64), 3.85 (2.36-6.28) and 6.35 (2.20-18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. CONCLUSIONS Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.
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Affiliation(s)
- Minkyo Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Gwen Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Neal D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Jill Koshiol
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Rachael Z. Stolzenberg-Solomon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Christian C. Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Satu Männistö
- Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Charles S. Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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Wang C, Song DJ, Xu ZL, Xie SP, Hu JH. A network meta-analysis of the short-term efficacy of five chemotherapy regimens based on cisplatin and fluorouracil for esophagogastric junctional adenocarcinoma. Exp Mol Med 2017; 49:e383. [PMID: 28960212 PMCID: PMC5628279 DOI: 10.1038/emm.2017.170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Revised: 03/31/2017] [Accepted: 04/07/2017] [Indexed: 12/16/2022] Open
Abstract
The primary purpose of this study was to explore the short-term efficacy of different cisplatin and fluorouracil-based chemotherapy regimens in the treatment of patients with esophagogastric junctional adenocarcinoma (EGJA) using a network meta-analysis (NMA). Randomized controlled trials (RCTs) related to chemotherapy regimens based on cisplatin and fluorouracil for EGJA were included from the PubMed, EMBASE and Cochrane Library electronic databases (from inception to June 2016). Direct and indirect evidence were combined to calculate the pooled odds ratio (OR) and its 95% confidence interval (95% CI) as well as to draw the surface under the cumulative ranking (SUCRA) curves. This NMA finally enrolled ten eligible RCTs with the following five regimens: cisplatin plus fluorouracil (cisplatin+fluorouracil), cisplatin+fluorouracil-based chemotherapy (cisplatin+fluorouracil+docetaxel/epirubicin/irinotecan), fluorouracil-based chemotherapy (fluorouracil+docetaxel/doxorubicin/methotrexate/irinotecan), cisplatin-based chemotherapy (cisplatin+docetaxel/epirubicin/irinotecan/capecitabine/s-1) and other drug-based chemotherapy (docetaxel/irinotecan/capecitabine). These results revealed that compared with a cisplatin+ fluorouracil-based chemotherapy regimen, the fluorouracil-based chemotherapy regimen had a lower overall response rate (ORR) and partial response (PR) for EGJA patients (ORR: OR=0.43, 95% CI=0.22-0.86; PR: OR=0.46, 95% CI=0.23-0.91). Cluster analyses suggested that the cisplatin+fluorouracil-based chemotherapy regimen had the best short-term efficacy for EGJA in terms of the complete response (CR), PR, ORR, stable disease (SD) and progression disease (PD). Our results indicated that cisplatin+fluorouracil-based chemotherapy regimens may have the best short-term efficacy in the treatment of EGJA.
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Affiliation(s)
- Cong Wang
- Department of Administration and Management, School of Humanities and Social Sciences, Beihang University, Beijing, China
| | - Dong-Jian Song
- Department of Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhi-Li Xu
- Department of Administration and Management, School of Humanities and Social Sciences, Beihang University, Beijing, China
| | - Shu-Ping Xie
- Department of General Surgery, Huaihe Hospital, Henan University, Kaifeng, China
| | - Jun-Hong Hu
- Department of General Surgery, Huaihe Hospital, Henan University, Kaifeng, China
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12
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Jiang T, Zhang H, Liu X, Song H, Yao R, Li J, Zhao Y. Effect of oxaliplatin combined with polyenephosphatidylcholine on the proliferation of human gastric cancer SGC-7901 cells. Oncol Lett 2017; 12:4538-4546. [PMID: 28101212 PMCID: PMC5228078 DOI: 10.3892/ol.2016.5293] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 09/02/2016] [Indexed: 01/27/2023] Open
Abstract
Oxaliplatin (L-OHP) is a platinum compound that is widely used to treat certain solid tumors, including gastric tumors. L-OHP is an effective anti-cancer treatment; however, its usage increases the probability of patients developing hepatic injury with inflammation, referred to as chemotherapy-associated steatohepatitis. The present study aimed to evaluate the outcome of L-OHP treatment combined with polyenephosphatidylcholine (PPC), a major component of essential phospholipids used to treat steatohepatitis, on SGC-7901 gastric cancer cell proliferation. This would help to determine whether combination therapy with L-OHP and PPC is clinically beneficial for patients with gastric cancer. The viability of SGC-7901 cells was verified by an MTT assay; flow cytometry was used to analyze the cell cycle and rates of cell apoptosis; oxidation-related indicators were measured by spectrophotometry, and the expression of cell cycle- and apoptosis-related proteins was determined by western blotting. The results demonstrated that L-OHP significantly inhibited SGC-7901 cell growth in a dose- and time-dependent manner (F=194.193, P<0.01 and F=12.428, P=0.01, respectively). Furthermore, PPC stimulated the growth of SGC-7901 cells and greatly promoted their apoptosis induced by L-OHP, which was supported by the upregulation of cytochrome c and the downstream activation of caspases 3 and 9. Finally, following treatment with a combination of PPC and L-OHP, the expression of cyclins D1 and E was downregulated; however, PPC did not alter the production of reactive oxygen species caused by L-OHP (P=0.88). The present study determined that the combination of L-OHP and PPC exerts a synergistic anti-tumor effect, suggesting that L-OHP and PPC combination therapy may be used as a treatment for patients with gastric cancer that reduces the side effects of L-OHP without inhibiting its efficacy.
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Affiliation(s)
- Tao Jiang
- School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China; Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Hongjun Zhang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Xiguang Liu
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Hao Song
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Ruyong Yao
- Department of Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Jianbin Li
- Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Yuanyuan Zhao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
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Rim C, Lee JA, Gong S, Kang DW, Yang H, Han HY, Kim NY. A Case of Long-Term Complete Remission of Advanced Gastric Adenocarcinoma with Liver Metastasis. J Gastric Cancer 2016; 16:115-9. [PMID: 27433398 PMCID: PMC4944000 DOI: 10.5230/jgc.2016.16.2.115] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 04/30/2016] [Accepted: 04/30/2016] [Indexed: 12/18/2022] Open
Abstract
We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery.
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Affiliation(s)
- Ch'angbum Rim
- Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea
| | - Jung-Ae Lee
- Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea
| | - Soojung Gong
- Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea
| | - Dong Wook Kang
- Department of Pathology, Eulji University Hospital, Daejeon, Korea
| | - Heebum Yang
- Department of Emergency Medicine, Eulji University Hospital, Daejeon, Korea
| | - Hyun Young Han
- Department of Radiology, Eulji University Hospital, Daejeon, Korea
| | - Nae Yu Kim
- Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea
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Wang L, Song Q, Li J, Chen X. S-1 treatment leading to complete remission of advanced duodenal adenocarcinoma: A case report. Mol Clin Oncol 2015; 3:1184-1186. [PMID: 26623074 DOI: 10.3892/mco.2015.607] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Accepted: 07/09/2015] [Indexed: 12/29/2022] Open
Abstract
Primary duodenal adenocarcinoma (DA) is a rare malignant neoplasm, accounting for 1% of all gastrointestinal tract carcinomas. This is the case report of a 40-year-old male patient with a duodenal lesion detected on abdominal magnetic resonance imaging and diagnosed by endoscopy and biopsy as DA. Following surgical resection and histopathological examination, the tumor was confirmed as differentiated duodenal neuroendocrine carcinoma with liver metastasis (TxNxM1). The patient received 8 cycles of palliative chemotherapy with oxaliplatin and S-1 and achieved a clinically complete response, with a treatment-related toxicity profile that was considered as tolerable. Therefore, this regimen exhibited favorable efficacy and a tolerable toxicity profile for the treatment of DA in this case.
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Affiliation(s)
- Lijun Wang
- Department of Computerized Tomography, Shandong Medical Sciences, Jinan, Shandong 250000, P.R. China
| | - Quanmao Song
- Oncology Department, PKU Care Luzhong Hospital, Zibo, Shandong 255000, P.R. China
| | - Jinpeng Li
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Xiaohua Chen
- Oncology Department, PKU Care Luzhong Hospital, Zibo, Shandong 255000, P.R. China
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15
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Karve S, Lorenzo M, Liepa AM, Hess LM, Kaye JA, Calingaert B. Treatment Patterns, Costs, and Survival among Medicare-Enrolled Elderly Patients Diagnosed with Advanced Stage Gastric Cancer: Analysis of a Linked Population-Based Cancer Registry and Administrative Claims Database. J Gastric Cancer 2015; 15:87-104. [PMID: 26161282 PMCID: PMC4496446 DOI: 10.5230/jgc.2015.15.2.87] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 03/28/2015] [Accepted: 04/13/2015] [Indexed: 01/29/2023] Open
Abstract
PURPOSE To assess real-world treatment patterns, health care utilization, costs, and survival among Medicare enrollees with locally advanced/unresectable or metastatic gastric cancer receiving standard first-line chemotherapy. MATERIALS AND METHODS This was a retrospective analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database (2000~2009). The inclusion criteria were as follows: (1) first diagnosed with locally advanced/unresectable or metastatic gastric cancer between July 1, 2000 and December 31, 2007 (first diagnosis defined the index date); (2) ≥65 years of age at index; (3) continuously enrolled in Medicare Part A and B from 6 months before index through the end of follow-up, defined by death or the database end date (December 31, 2009), whichever occurred first; and (4) received first-line treatment with fluoropyrimidine and/or a platinum chemo-therapy agent. RESULTS In total, 2,583 patients met the inclusion criteria. The mean age at index was 74.8±6.0 years. Over 90% of patients died during follow-up, with a median survival of 361 days for the overall post-index period and 167 days for the period after the completion of first-line chemotherapy. The mean total gastric cancer-related cost per patient over the entire post-index follow-up period was United States dollar (USD) 70,808±56,620. Following the completion of first-line chemotherapy, patients receiving further cancer-directed treatment had USD 25,216 additional disease-related costs versus patients receiving supportive care only (P<0.001). CONCLUSIONS The economic burden of advanced gastric cancer is substantial. Extrapolating based on published incidence estimates and staging distributions, the estimated total disease-related lifetime cost to Medicare for the roughly 22,200 patients expected to be diagnosed with this disease in 2014 approaches USD 300 millions.
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Affiliation(s)
- Sudeep Karve
- RTI Health Solutions, Research Triangle Park, NC, USA
| | | | | | - Lisa M Hess
- Eli Lilly and Company, Indianapolis, IN, USA
| | - James A Kaye
- RTI Health Solutions, Research Triangle Park, NC, USA
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16
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Combination Chemotherapy with S-1 and Oxaliplatin (SOX) as First-Line Treatment in Elderly Patients with Advanced Gastric Cancer. Pathol Oncol Res 2015; 21:867-73. [PMID: 25648439 DOI: 10.1007/s12253-015-9903-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Accepted: 01/09/2015] [Indexed: 01/29/2023]
Abstract
This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m(2) oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3-63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8-87.8 %). The median follow-up period was 23 months (range, 5-42 months). The median time to progression was 6.9 months (95 %CI, 5.5-8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4-14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7-66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and well-tolerated regimen for elderly patients with advanced gastric cancer.
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Chen X, Wang G, Lu X, Gao P, Song Y, Sun J, Li A, Xu Y, Xu H, Wang Z. Polymorphisms and haplotypes of the miR-148/152 family are associated with the risk and clinicopathological features of gastric cancer in a Northern Chinese population. Mutagenesis 2014; 29:401-7. [PMID: 25261463 DOI: 10.1093/mutage/geu050] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Our previous studies showed that the expressions of miR-148a, miR-152 and miR-148b are altered in gastric cancer (GC). The present study aimed to find relationship between individual single nucleotide polymorphisms (SNPs) or haplotypes of these miRNAs and susceptibility, clinicopathological parameters and prognosis of GC in a large sample of the Han population of Northern China. Twelve SNPs were genotyped using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry in a case-control study of 571 Chinese GC patients and 571 cancer-free controls. The rs11170877 G allele (P = 0.027) and the rs12231393 C allele (P = 0.034) were associated with a decreased risk of GC. However, these associations were lost after Bonferroni correction. The rs4719839 G allele was associated with Borrmann type III-IV GC (P = 0.034), increased tumour size (P = 0.020), an increased rate of lymph node metastasis (P = 0.047) and advanced TNM stage (P = 0.009). These associations were also lost after Bonferroni correction. The haplotype of miR-148b was significantly correlated with GC risk. The haplotypes in miRNA-148a were different in Borrmann types. The haplotype of miR-152 distributed various in the positive lymphovascular invasion group compared to negative group. Polymorphisms of miR-148b rs11170877 and 12231393 and their haplotypes were predictive factors of susceptibility to GC. A functional genetic variant of miRNA rs4719839 and the corresponding haplotype were associated with clinicopathological features and prognosis of advanced GCs.
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Affiliation(s)
- Xiaowan Chen
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Guoli Wang
- Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Xiaoli Lu
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Peng Gao
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Yongxi Song
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Jingxu Sun
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Ailin Li
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Yingying Xu
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Huimian Xu
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China and Department of Biochemistry and Molecular Biology, China Medical University, 92 North 2nd Road, Heping District, Shenyang 110001, China
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18
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Zhang ZD, Kong Y, Yang W, Zhang B, Zhang YL, Ma EM, Liu HX, Chen XB, Hua YW. Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer. World J Surg Oncol 2014; 12:115. [PMID: 24758484 PMCID: PMC4020605 DOI: 10.1186/1477-7819-12-115] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 04/07/2014] [Indexed: 02/21/2023] Open
Abstract
Background The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer. Methods For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate. Results There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P = 0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P = 0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P = 0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P = 0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups. Conclusions These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Ya-Wei Hua
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou 45008, China.
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Zhang ZD, Kong Y, Yang W, Zhang B, Zhang YL, Ma EM, Liu HX, Chen XB, Hua YW. Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer. World J Surg Oncol 2014. [PMID: 24758484 DOI: 10.1186/1477-7819-] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer. METHODS For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate. RESULTS There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups. CONCLUSIONS These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Ya-Wei Hua
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou 45008, China.
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20
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Coupe NA, Karikios D, Chong S, Yap J, Ng W, Merrett N, Lin M. Metabolic information on staging FDG-PET-CT as a prognostic tool in the evaluation of 97 patients with gastric cancer. Ann Nucl Med 2014; 28:128-135. [PMID: 24297388 DOI: 10.1007/s12149-013-0791-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2013] [Accepted: 11/10/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVE Gastric cancer remains a leading cause of malignancy-related mortality. Many patients with locally advanced disease succumb despite peri-operative chemotherapy and the survival benefit of chemotherapy for advanced disease is modest, suggesting that current staging is imperfect. The role of fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging of gastric cancer remains to be determined. This study aimed to determine, and compare with computerized tomography (CT), the association between FDG-PET uptake in the primary tumour and regional lymph nodes, and overall survival in patients with all stage gastric cancer. METHODS Patients with histologically confirmed gastric cancer (any stage) who, at diagnosis, had received a staging FDG-PET-CT at our institution between 2006 and 2011 were included. Records were retrospectively analysed. Patients with >50 % of tumour above the gastro-oesophageal junction or an active second malignancy were excluded. RESULTS 97 patients were included in the analysis. Surgery with curative intent was performed in 68 patients. In univariate analysis, an association with overall survival was seen in patients who had FDG-PET-positive primary tumours (hazard ratio (HR) for death 3.33, 95 % confidence interval (95 % CI) 1.63-6.80, p = 0.001). FDG-PET lymph node positive (vs node negativity) was associated with inferior overall survival (HR 8.66, 95 % CI 4.59-16.37, p < 0.0001), and remained an independent predictor in the multivariate analysis. In contrast, positive lymphadenopathy identified on CT was not associated with overall survival (HR 1.34, 95 % CI 0.79-2.29, p = 0.82). CONCLUSION FDG-PET-positive tumours are associated with an inferior overall survival. In contrast to CT, FDG-PET-positive lymphadenopathy is associated with a decreased overall survival.
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Affiliation(s)
- Nicholas A Coupe
- Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia,
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Chen S, Zheng Z, Tang J, Lin X, Wang X, Lin J. Association of polymorphisms and haplotype in the region of TRIT1, MYCL1 and MFSD2A with the risk and clinicopathological features of gastric cancer in a southeast Chinese population. Carcinogenesis 2013; 34:1018-24. [PMID: 23349019 DOI: 10.1093/carcin/bgt010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
To explore the association of polymorphisms in the region of three neighboring genes TRIT1, MYCL1 and MFSD2A with risk and clinicopathological features of gastric cancer, 19 tagging SNPs in this region were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in a case-control study of 610 Chinese gastric cancer patients and 608 cancer-free controls. MFSD2A rs4233508 T>C CC genotype was associated with an increased risk of gastric cancer in younger patients and an increased risk of moderately/well-differentiated intestinal-type gastric cancer (adjusted odds ratio [OR], 1.74 and 1.50, respectively). TRIT1 rs11581557 T>G TG was associated with lymph node metastasis (TG versus TT/GG, adjusted OR, 1.64). MFSD2A rs12083239 GC genotype and TRIT1 rs2172362 or rs230310 homozygous genotype were associated with Lauren's classification (GC versus GG, adjusted OR, 1.69; GC versus GG/CC, adjusted OR, 1.74) and tumor site (rs2172362: CC versus CT, adjusted OR, 1.71; CC/TT versus CT, adjusted OR, 1.62; rs230310: CC versus CT, adjusted OR, 1.75; CC/TT versus CT, adjusted OR, 1.67) of gastric cancer, respectively. One TRIT1 haplotype, CCGT, was associated with lymph node metastasis and tumor site of gastric cancer (CCGT versus TTTT, adjusted OR, 1.91 and 1.55). This is believed to be the first report that several tagging SNPs and haplotypes in TRIT1, MYCL1 and MFSD2A region are significantly associated with risk and clinicopathological features of gastric cancer in a Chinese population. The findings might be useful for risk assessment and prognosis prediction of gastric cancer.
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Affiliation(s)
- Shuqin Chen
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center of Molecular Medicine, Fujian Medical University, Fuzhou, 350004, China
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Zayakin P, Ancāns G, Siliņa K, Meistere I, Kalniņa Z, Andrejeva D, Endzeliņš E, Ivanova L, Pismennaja A, Ruskule A, Doniņa S, Wex T, Malfertheiner P, Leja M, Linē A. Tumor-associated autoantibody signature for the early detection of gastric cancer. Int J Cancer 2012; 132:137-47. [PMID: 22684876 DOI: 10.1002/ijc.27667] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2012] [Accepted: 05/10/2012] [Indexed: 12/12/2022]
Abstract
Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150-feature microarray was tested with sera from 100 patients with GC and 100 cancer-free controls, and then the top-ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45-autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.
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Affiliation(s)
- Pawel Zayakin
- Latvian Biomedical Research and Study Centre, Riga, Latvia
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23
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Lin KY, Wang LH, Hseu YC, Fang CL, Yang HL, Kumar KJS, Tai C, Uen YH. Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. Mol Cancer Res 2012; 10:750-9. [PMID: 22544459 DOI: 10.1158/1541-7786.mcr-11-0598-t] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Although gastric cancer is one of the most common malignancies worldwide, little is known on the molecular process of its development and progression. This study investigates the involvement of guanine nucleotide exchange factor Vav3 in tumor progression and in the prognosis of human gastric cancer. The two patient cohorts in this study consisted of 167 gastric cancer cases from 1997 through 2001, documenting pathologic and clinical factors, as well as the clinical outcomes. Immunohistochemistry, reverse transcription PCR, immunoblotting, and immunofluorescence were used to examine Vav3 expression in tumor and nontumor pairs of gastric tissues and gastric cell lines. Small hairpin RNA (shRNA) technology was used to study the effects of Vav3 knockdown on the growth and spread of gastric cancer cells. Finally, xenograph proliferation was used to study the tumor growth. Overexpression of Vav3 was associated with the depth of invasion (P = 0.0004), nodal status (P = 0.0260), distant metastasis (P = 0.0003), stage (P = 0.0002), and vascular invasion (P = 0.0286); and correlated with poor disease-free survival (P < 0.0001). Multivariate Cox regression analysis shows that overexpression of Vav3 is an independent prognostic marker for gastric cancer (P = 0.033). Disrupting the expression of Vav3 using shRNA technology inhibited gastric cancer cell growth, spread, and xenograph proliferation. This study suggests that overexpression of Vav3 can be a useful marker for predicting the outcome of patients with gastric cancer and that Vav3 targeting can represent a potential modality for treating gastric cancer.
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Affiliation(s)
- Kai-Yuan Lin
- Department of Medical Research, Chi Mei Hospital Chiali, 606, Shin-Hwa Road, Chiali District, Tainan 722, Taiwan
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24
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Gao SG, Jia RN, Feng XS, Xie XH, Shan TY, Pan LX, Song NS, Wang YF, Ding KL, Wang LD. Therapeutic effects of combined oxaliplatin and S-1 in older patients with advanced gastric cardiac adenocarcinoma. World J Gastroenterol 2011; 17:5221-6. [PMID: 22215948 PMCID: PMC3243890 DOI: 10.3748/wjg.v17.i47.5221] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2011] [Revised: 03/29/2011] [Accepted: 04/05/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA).
METHODS: Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m2 po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m2 iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeated for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed.
RESULTS: The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ2 = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ2 = 0.032 and P = 0.857). Efficacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ2 = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05).
CONCLUSION: The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.
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25
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Matsumoto K, Kitanaka A, Uemura M, Waki F, Fukumoto T, Ohnishi H, Kubota Y, Ishida T. S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13). World J Gastroenterol 2011; 17:4632-4. [PMID: 22147971 PMCID: PMC3225100 DOI: 10.3748/wjg.v17.i41.4632] [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: 01/05/2011] [Revised: 03/07/2011] [Accepted: 03/14/2011] [Indexed: 02/06/2023] Open
Abstract
Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration, and that hematological adverse events were relatively rare. Pyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-II inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia.
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26
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Li R, Yuan L, Wang J, Wang J. Co-expression of erythropoietin receptor with human epidermal growth factor 2 may counteract trastuzumab inhibition in gastric cancer. Med Hypotheses 2011; 77:948-52. [PMID: 21944379 DOI: 10.1016/j.mehy.2011.07.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2011] [Accepted: 07/07/2011] [Indexed: 02/06/2023]
Abstract
Gastric cancer has high prevalence and high modality worldwide. For many years, few improvements in the efficacy of treatments were reported for advanced gastric cancer settings. Although a novel molecular target agent trastuzumab, in combination with chemotherapy, prolongs overall survival time in advanced gastric cancer, resistance to this drug still exists among human epidermal growth factor receptor-2 (HER2) positive patients. HER2 and erythropoietin receptor (EPOR) downstream signaling pathway have some common factors like Akt, Erk and STATs. Also there exist evidences that EPOR may express on some solid tumors and probably promote tumor progression. So it is reasonable for us to hypothesis that HER2 and EPOR may be co-expressed in the same gastric cancer cell and if so, EPOR signaling pathway may overlaps that with HER2 and promotes HER2 induced signal transduction to cell proliferation. In clinical settings, a stimulation of EPOR will play antagonistic effects on trastuzumab-induced anti-tumor activity to HER2-positive gastric cancer patients. Co-expression of EPOR and HER2 is a predictive factor for resistance of trastuzumab in gastric cancer.
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Affiliation(s)
- Rui Li
- Department of Medical Oncology, Changzheng Hospital, The Second Military Medical University, No 64, Hetian Road, Shanghai 200070, China.
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27
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Iwase H, Shimada M, Tsuzuki T, Ina K, Sugihara M, Haruta J, Shinoda M, Kumada T, Goto H. A phase II multi-center study of triple therapy with paclitaxel, S-1 and cisplatin in patients with advanced gastric cancer. Oncology 2011; 80:76-83. [PMID: 21659786 DOI: 10.1159/000328746] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 03/29/2011] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. METHODS A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle. RESULTS All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. CONCLUSIONS Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.
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Affiliation(s)
- H Iwase
- Nagoya Medical Centre, Nagoya, Japan.
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28
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Kim ST, Lee J, Lee KT, Lee JK, Lee KH, Choi SH, Heo JS, Choi DW, Park SH, Park JO, Lim HY, Park YS, Kang WK. The efficacy of frontline platinum-based combination chemotherapy in advanced adenocarcinoma of the ampulla of Vater. Med Oncol 2010; 27:1149-1154. [PMID: 19898973 DOI: 10.1007/s12032-009-9351-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2009] [Accepted: 10/22/2009] [Indexed: 12/16/2022]
Abstract
Adenocarcinoma arising from the ampulla of Vater is a rare neoplasm that accounts for only 0.2% of all gastrointestinal tract malignancies and has limited data regarding its frontline therapy. We investigated the treatment outcomes in patients with advanced adenocarcinoma of the ampulla of Vater receiving frontline cisplatin-based combination chemotherapy. We analyzed 29 patients with advanced adenocarcinoma of the ampulla of Vater who had been treated by frontline cisplatin-based combination chemotherapy between June 2003 and April 2008. The chemotherapeutic agent added to cisplatin was gemcitabine in 9 patients and fluorouracil (FU) in 20 patients (11; intravenous 5-FU and 9; oral 5-FU (capecitabine)). The median age of patients was 56 years (range, 36-78), and the median ECOG performance status was 1 (0-1). The confirmed overall response rate was 27.5%, and the disease control rate was 72.4%. In all patients, no complete responses and 8 partial responses were observed (overall response rate, 27.5%). Stable disease was observed in 13 patients (44.8%), and progressive disease in 5 patients (17.2%). The median time to progression (TTP) was 4.9 months (95% CI, 3.4-6.4), and the median overall survival (OS) was 12.5 months (95% CI, 10.6-14.4). There were no significant differences for TTP and OS according to the different chemotherapeutic agents added to cisplatin. Grade 3 or 4 hematologic toxicities included leukopenia in seven patients and thrombocytopenia in one patient. There were no grade 3 or 4 nonhematologic toxicities or treatment-related deaths. The cisplatin-based combination chemotherapy showed moderate activity and a favorable toxicity profile as a frontline treatment for patients with advanced adenocarcinoma of the ampulla of Vater.
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Affiliation(s)
- Seung Tae Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, South Korea.
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29
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Chung HW, Lee EJ, Cho YH, Yoon SY, So Y, Kim SY, Lee MH, Kim JH, Lee SY, Sung IK, Park HS, Yoo MW, Lee KY. High FDG uptake in PET/CT predicts worse prognosis in patients with metastatic gastric adenocarcinoma. J Cancer Res Clin Oncol 2010; 136:1929-35. [PMID: 20306088 DOI: 10.1007/s00432-010-0852-5] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2009] [Accepted: 02/17/2010] [Indexed: 12/20/2022]
Abstract
PURPOSE We evaluated the role of FDG-PET/CT in patients with metastatic gastric adenocarcinoma before palliative chemotherapy to predict prognosis and chemotherapeutic response. METHODS The study included 35 consecutive newly diagnosed patients with metastatic gastric adenocarcinoma who underwent FDG-PET/CT before palliative chemotherapy. Maximum standardized uptake value (SUVmax) of the primary tumor was assessed to evaluate survival and chemotherapeutic response. Survival analysis was performed for time to progression and overall survival using the Kaplan-Meier method. Cox proportional hazard models were used to determine independent prognostic factors. RESULTS All primary tumors were visualized using FDG-PET/CT (mean SUVmax = 8.1 ± 4.5, range 2.5-22.1). Sensitivity, specificity, and accuracy of FDG-PET/CT in detection of solid organ metastasis were 95.2% (20/21), 100% (14/14), and 97.1% (34/35), respectively. No significant difference of primary tumor SUVmax was found among the chemotherapeutic response groups. Univariate survival analysis demonstrated ECOG performance status (≥2), presence of solid organ metastasis, number of organs involved in distant metastasis (≥2), and SUVmax of the primary tumor (>8) as significant predictors for poor overall survival. Multivariate survival analysis showed SUVmax of the primary tumor (P = 0.048), presence of solid organ metastasis (P = 0.015), and ECOG performance status (P = 0.002) as significant independent prognostic predictors for overall survival. CONCLUSIONS High FDG uptake of the primary tumor in patients with metastatic gastric adenocarcinoma is associated with poor overall survival. Assessment of tumor FDG uptake has limited value for prediction of chemotherapeutic response, but provides useful information regarding prognosis.
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Affiliation(s)
- Hyun Woo Chung
- Department of Nuclear Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, 4-12 Hwayang-dong, Kwangjin-gu, Seoul, Korea.
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30
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Gao J, Sai N, Wang C, Sheng X, Shao Q, Zhou C, Shi Y, Sun S, Qu X, Zhu C. Overexpression of chromokinesin KIF4 inhibits proliferation of human gastric carcinoma cells both in vitro and in vivo. Tumour Biol 2010; 32:53-61. [PMID: 20711700 DOI: 10.1007/s13277-010-0090-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2010] [Accepted: 07/26/2010] [Indexed: 01/05/2023] Open
Abstract
Gastric carcinoma is a common type of malignant tumors and is associated with high death rates. The pathogenesis of gastric carcinoma is still unclear, and increasing evidence shows that many factors contribute to this process. Chromokinesin KIF4 is involved in multiple critical cellular processes. Recently, it has become apparent that KIF4 plays a crucial suppressive role in tumorigenesis. However, the role of KIF4 in human gastric cancer is still unclear. In this study, we examined expression profiles of KIF4 in gastric carcinoma specimens and generated gastric cancer cells that stably express GFP-KIF4 fusion protein (designated as BGC-GFP-KIF4 cells) followed by cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and soft agar colony-formation assays. Simultaneously, we further examined the capability of tumor formation of BGC-GFP-KIF4 cells in nude mice. The results showed that among 23 gastric carcinoma specimens, 13 cases (56.6%) had lower expression of KIF4 compared with corresponding adjacent tissues. In addition, there was a significant correlation between low expression of KIF4 and poor differentiation of tumor (P = 0.024). Overexpression of KIF4 in BGC cells inhibited cell proliferation in vitro, as well as their ability to form tumors in vivo. Our findings suggest that human chromokinesin KIF4 functions as an inhibitor of gastric cancer cell proliferation and might serve as a novel biological target to cure human gastric carcinoma.
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Affiliation(s)
- Jie Gao
- College of Life Science/Tianjin Key Laboratory of Cyto-Genetical and Molecular Regulation, Tianjin Normal University, Tianjin 300387, China
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31
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Verwimp J, Geurs F, Ponette S, Ponette J, Martens J, Bulté K. Complete response of a metastatic gastroesophageal adenocarcinoma on irinotecan-based chemotherapy in a dialysis patient. Int J Nephrol Renovasc Dis 2010; 3:61-4. [PMID: 21694930 PMCID: PMC3108765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2010] [Indexed: 12/05/2022] Open
Abstract
We present the first case report of a complete response of metastatic gastroesophageal cancer in a chronic hemodialysis patient with irinotecan-based chemotherapy. An elderly dialysis patient presented with diffuse liver metastases by a gastroesophageal adenocarcinoma. He received combination chemotherapy with 5 fluorouracil and irinotecan. After six months of chemotherapy, liver scans show complete remission. The principles, practice, and experience of chemotherapy with irinotecan during dialysis are discussed.
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Affiliation(s)
| | - F Geurs
- Department of Medical Oncology,Correspondence: Filip Geurs, Department of Medical Oncology, Regionaal Ziekenhuis Sint-Maria, Ziekenhuislaan, 100, 1500 Halle, Belgium, Tel +32 2 363 6610, Fax +32 2 363 6264, Email
| | | | | | - J Martens
- Department of Nephrology, Regionaal Ziekenhuis Sint-Maria, Ziekenhuislaan, Halle, Belgium
| | - K Bulté
- Department of Gastroenterology
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Abstract
Host defence peptides (HDP) produced by almost all species of living organisms and widely recognized as antimicrobial antibiotics have also proved to be capable of killing a wide variety of cancer cells. In this respect they have many advantages over conventional cytotoxic chemotherapeutic agents. They seem to kill cancer cells by effects on plasma membranes and/or the membranes of mitochondria. They are often effective against multidrug-resistant cells. They have a broad spectrum of activity in that their killing effects are not restricted to particular kinds of cancer. Above all they commonly have few side effects in that they do not have the same detrimental effects on normal cells as they do on cancer cells. It has been demonstrated that HDP can be used as effective adjuvants to conventional chemotherapeutic agents. In addition they have effects on neo-angiogenesis which is important in relation to tumour growth. HDP have been shown to be powerful immunomodulators in a number of circumstances and in this respect they are believed to be instrumental in strengthening immunological host defence against cancer cells. Importantly it has also been shown that certain HDP have the capability to alter the capacity of cells to import Ca ions by affecting the location and thus function of calreticulin. Such changes it has been argued are significant in facilitating the killing of tumour cells by immunogical means. HDP constitute a novel class of anticancer agents for which, as we develop better knowledge of their pharmacokinetic profiles and learn better how to tailor their administration, hold high promise to augment or even replace the currently available cytotoxic anticancer chemotherapeutic agents most of which owe their efficacy to their capacity to bind to and damage target cell DNA.
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Affiliation(s)
- Károly Lapis
- Semmelweis Egyetem, AOK I. sz. Patológiai és Kísérleti Rákkutató Intézet, 1085 Budapest, Ulloi út 26.
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Nishiyama M, Wada S. Docetaxel: its role in current and future treatments for advanced gastric cancer. Gastric Cancer 2010; 12:132-41. [PMID: 19890692 DOI: 10.1007/s10120-009-0521-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2009] [Accepted: 08/06/2009] [Indexed: 02/07/2023]
Abstract
A globally accepted standard chemotherapy remains undetermined in gastric cancer, but the recent introduction of active "new-generation agents" such as taxanes, irinotecan (CPT-11), oxaliplatin, S-1, and capecitabine, offers hope for markedly improving patient outcomes. Docetaxel, as well as the other new-generation agents, plays a key role in the development of the new-era chemotherapy, and the incorporation of taxanes has provided several regimens, such as docetaxel/cisplatin/5-fluorouracil (5-FU) (DCF), that could become standard treatment. The DCF regimen is now regarded as a standard treatment option in advanced gastric cancer in selected patients in good condition. Many institutions and cooperative groups continue to study a variety of docetaxel-based combinations with "new-generation cytotoxic agents" in various treatment settings, and recent attention has been focused on the incorporation of biological agents, such as cetuximab, bevacizumab, everolimus, and sunitinib, into docetaxel-containing combinations as another innovative approach. The ongoing clinical trials of a number of new regimens will clarify their clinical benefits in gastric cancer treatment. Along with the development of more active docetaxel combination regimens, the identification of predictive biomarkers for each regimen has been intensively studied recently. This review focuses on docetaxel as a key agent in gastric cancer chemotherapy, and discusses the role of this taxane in current and future treatments for advanced gastric cancer.
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Affiliation(s)
- Masahiko Nishiyama
- Translational Research Center, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
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