|
1
|
A phase II trial of concurrent 3D-CRT/IMRT and oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) in gastric cancer patients with R0 gastrectomy and D2 lymph node dissection. Gastric Cancer 2016; 19:245-54. [PMID: 25609451 DOI: 10.1007/s10120-015-0461-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 12/29/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND To evaluate the safety and efficacy of a concurrent three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) plus oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) regimen in completely resected gastric cancer patients with D2 lymph node dissection. MATERIALS AND METHODS Patients with stage IB-IIIC gastric cancer (per the AJCC, 7th edition) who had undergone R0 and D2 gastrectomy were recruited. Two cycles of FOLFOX with concurrent 3D-CRT or IMRT (50.4 Gy/28f) were administered. One and an additional five cycles of FOLFOX were delivered before and after concurrent chemoradiotherapy, respectively. Primary endpoints were relapse-free survival (RFS) and overall survival (OS), with adverse events as secondary endpoints. RESULTS From 2008 to 2011, 110 patients were evaluable. The 1-, 2- and 3-year RFS and OS were 86.2, 72.2, 67.8 and 94.7, 87.2, 77.6%, respectively. On multivariate analysis, stage (≤ IIIA vs. >IIIA) was a statistically significant factor affecting both RFS and OS. Additionally, the T-category (≤ T4a vs. = T4b) was a statistically significant factor affecting only the RFS. The most commonly observed grade 3 or 4 adverse events were nausea and vomiting, decreased appetite, leukopenia/neutropenia and fatigue, each of which occurred in 14.5, 11.8, 9.1 and 6.4% patients, respectively. CONCLUSIONS Adjuvant 3D-CRT/IMRT to a dose of 50.4 Gy/28f with concurrent FOLFOX is safe and effective in patients following radical gastrectomy with D2 lymph node dissection.
Collapse
|
|
2
|
Shen X, Si Y, Yang Z, Wang Q, Yuan J, Zhang X. MicroRNA-542-3p suppresses cell growth of gastric cancer cells via targeting oncogene astrocyte-elevated gene-1. Med Oncol 2014; 32:361. [PMID: 25432696 DOI: 10.1007/s12032-014-0361-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 11/13/2014] [Indexed: 12/21/2022]
Abstract
MicroRNAs (miRNAs) have been suggested to play critical roles in tumorigenesis as well as in the development of therapies for the treatment of cancers. However, the tumor-associated miRNAs in gastric cancers remain poorly understood. Here, we report on miR-542-3p in gastric cancers, which has been widely studied in other cancers as a tumor suppressor. Real-time quantitative PCR analysis demonstrated that miR-542-3p was significantly down-regulated in gastric cancer tissues (p < 0.0001) and cell lines (p < 0.001). Overexpression of miR-542-3p significantly inhibited cell growth of gastric cancer cells both in vitro (p < 0.01) and in vivo (p < 0.01). Notably, overexpression of miR-542-3p apparently reduced the protein expression of astrocyte-elevated gene-1 (AEG-1) (p < 0.01). The dual-luciferase reporter assay validated that miR-542-3p directly bound the 3'-untranslated region (UTR) of AEG-1, which could be abolished by mutation of the predicted miR-542-3p binding site. Furthermore, overexpression of miR-542-3p markedly inhibited the activation of oncogenic signaling pathways including the Akt, β-catenin and nuclear factor-κB pathways. Additionally, overexpression of AEG-1 without the 3'-UTR partially reversed the cell growth arrest induced by miR-542-3p overexpression in gastric cancer cells (p < 0.05). Taken together, these data suggest that miR-542-3p might function as a tumor suppressor in gastric cancer, potentially by targeting the oncogene AEG-1, implying a potential role for miR-542-3p in the development of therapeutic methods for gastric cancer.
Collapse
Affiliation(s)
- Xinsheng Shen
- Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | | | | | | | | | | |
Collapse
|
|
3
|
Shi H, Ji M, Wu J, Zhou Q, Li X, Li Z, Zheng X, Xu B, Zhao W, Wu C, Jiang J. Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer. World J Surg Oncol 2014; 12:188. [PMID: 24947047 PMCID: PMC4076248 DOI: 10.1186/1477-7819-12-188] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 06/08/2014] [Indexed: 12/24/2022] Open
Abstract
Background B7-H4 is a novel B7 ligand that plays an important role in the T cell-mediated immune response as a negative regulator. Previous studies have suggested the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in circulation and to investigate the correlations between sB7-H4 levels and clinicopathological parameters as well as the survival rate of patients with gastric cancer. Methods Blood specimens from 132 patients with gastric cancer and 63 healthy volunteers were analyzed by sandwich enzyme-linked immunosorbent assay. Results Median concentrations of sB7-H4 in patients with gastric cancer were significantly higher than those in healthy volunteers (16.85 versus 10.46 ng/mL; P = 0.008). Median levels of sB7-H4 were significantly correlated with tumor size, lymph node metastasis, the depth of tumor invasion and tumor-node-metastasis classification (P = 0.002, P = 0.001, P = 0.041 and P <0.001, respectively), but not with sex, age, tumor location or histological subtype (all P >0.05). Additionally, the overall survival rate was significantly lower in patients with high sB7-H4 levels when compared with low sB7-H4 levels (50.0% versus 77.3%, χ2 = 10.78, P = 0.001). Moreover, multivariate analysis demonstrated that the risk of death was significantly higher in patients with high sB7-H4 levels than in those with low sB7-H4 levels (P = 0.039). Conclusions sB7-H4 is a valuable blood marker for predicting the progression and prognosis of patients with gastric cancer.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Changping Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, Jiangsu Province, People's Republic of China.
| | | |
Collapse
|
|
4
|
Orditura M, Galizia G, Di Martino N, Ancona E, Castoro C, Pacelli R, Morgillo F, Rossetti S, Gambardella V, Farella A, Laterza MM, Ruol A, Fabozzi A, Napolitano V, Iovino F, Lieto E, Fei L, Conzo G, Ciardiello F, De Vita F. Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma-a pilot study. ACTA ACUST UNITED AC 2014; 21:125-33. [PMID: 24940093 DOI: 10.3747/co.21.1570] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. METHODS We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. RESULTS All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. CONCLUSIONS In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.
Collapse
Affiliation(s)
- M Orditura
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - G Galizia
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - N Di Martino
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - E Ancona
- Division of General Surgery 1, University of Padua, School of Medicine, Padua, Italy
| | - C Castoro
- Division of General Surgery 1, University of Padua, School of Medicine, Padua, Italy
| | - R Pacelli
- Division of Radiotherapy, Federico ii University of Naples School of Medicine, Naples, Italy
| | - F Morgillo
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - S Rossetti
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - V Gambardella
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - A Farella
- Division of Radiotherapy, Federico ii University of Naples School of Medicine, Naples, Italy
| | - M M Laterza
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - A Ruol
- Division of General Surgery 1, University of Padua, School of Medicine, Padua, Italy
| | - A Fabozzi
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - V Napolitano
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - F Iovino
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - E Lieto
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - L Fei
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - G Conzo
- Divisions of Surgical Oncology, Department of Anesthesiologic, Surgical, and Emergency Sciences, Second University of Naples School of Medicine, Naples, Italy
| | - F Ciardiello
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| | - F De Vita
- Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy
| |
Collapse
|
|
5
|
Capecitabine in adjuvant radiochemotherapy for gastric adenocarcinoma. Radiol Oncol 2014; 48:189-96. [PMID: 24991209 PMCID: PMC4078038 DOI: 10.2478/raon-2013-0065] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 08/13/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND In patients with non-metastatic gastric cancer surgery still remains the treatment of choice. Postoperative radiochemotherapy with 5-fluorouracil and leucovorin significantly improves the treatment outcome. The oral fluoropyrimidines, such as capecitabine, mimic continuous 5-fluorouracil infusion, are at least as effective as 5-fluorouracil, and such treatment is more comfortable for the patients. PATIENTS AND METHODS In the period from October 2006 to December 2009, 101 patients with gastric cancer in stages Ib-IIIc were treated with postoperative chemoradiation with capecitabine. Distal subtotal resection of the stomach was performed in 46.3%, total resection in 50.5% and multivisceral resection in 3.2% of patients. The main endpoints of this study were loco-regional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). The rates of acute side-effects were also estimated. RESULTS Seventy-seven percent of patients completed the treatment according to the protocol. The median follow-up time of all patients was 3.9 years (range: 0.4-6.3 years) and in survivors it was 4.7 years (range: 3.2-6.3 years). No death occurred due to the therapy. Acute toxicity, such as nausea and vomiting, stomatitis, diarrhoea, hand-foot syndrome and infections of grade 3 or 4, occurred in 5%, 1%, 2%, 8.9% and 18.8% of patients, respectively. On the close-out date 63.4% patients were still alive and with no signs of the disease. The 4-years follow-up survey showed that LRC, DFS, DSS and OS were 95.5%, 69.2%, 70.7%, and 66.2%, respectively. Higher pN-stage and splenectomy were found to be independent prognostic factors for all four types of survival and perineural invasion and lower treatment intensity for DFS, DSS and OS. CONCLUSIONS Postoperative radiochemotherapy with capecitabine is feasible, with low toxicity and the results of such treatment are good.
Collapse
|
|
6
|
Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F. Treatment of gastric cancer. World J Gastroenterol 2014; 20:1635-1649. [PMID: 24587643 PMCID: PMC3930964 DOI: 10.3748/wjg.v20.i7.1635] [Citation(s) in RCA: 482] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/29/2013] [Accepted: 11/12/2013] [Indexed: 02/06/2023] Open
Abstract
The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4(th) most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status.
Collapse
|
|
7
|
DE Sol A, Trastulli S, Grassi V, Corsi A, Barillaro I, Boccolini A, DI Patrizi MS, DI Rocco G, Santoro A, Cirocchi R, Boselli C, Redler A, Noya G, Kong SH. Requirement for a standardised definition of advanced gastric cancer. Oncol Lett 2013; 7:164-170. [PMID: 24348842 PMCID: PMC3861594 DOI: 10.3892/ol.2013.1672] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 08/23/2013] [Indexed: 01/14/2023] Open
Abstract
Each year, ~988,000 new cases of stomach cancer are reported worldwide. Uniformity for the definition of advanced gastric cancer (AGC) is required to ensure the improved management of patients. Various classifications do actually exist for gastric cancer, but the classification determined by lesion depth is extremely important, as it has been shown to correlate with patient prognosis; for example, early gastric cancer (EGC) has a favourable prognosis when compared with AGC. In the literature, the definition of EGC is clear, however, there is heterogeneity in the definition of AGC. In the current study, all parameters of the TNM classification for AGC reported in each previous study were individually analysed. It was necessary to perform a comprehensive systematic literature search of all previous studies that have reported a definition of ACG to guarantee homogeneity in the assessment of surgical outcome. It must be understood that the term ‘advanced gastric cancer’ may implicate a number of stages of disease, and studies must highlight the exact clinical TNM stages used for evaluation of the study.
Collapse
Affiliation(s)
- Angelo DE Sol
- Department of General Surgery, University of Perugia, St. Maria Hospital, Terni, Italy
| | - Stefano Trastulli
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Veronica Grassi
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Alessia Corsi
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Ivan Barillaro
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Andrea Boccolini
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Micol Sole DI Patrizi
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Giorgio DI Rocco
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Alberto Santoro
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Roberto Cirocchi
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Carlo Boselli
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Adriano Redler
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Giuseppe Noya
- Department of General and Oncological Surgery, University of Perugia, Perugia, Italy
| | - Seong-Ho Kong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
8
|
Huang W, Yang L, Liang S, Liu D, Chen X, Ma Z, Zhai S, Li P, Wang X. AEG-1 is a target of perifosine and is over-expressed in gastric dysplasia and cancers. Dig Dis Sci 2013; 58:2873-80. [PMID: 23912246 DOI: 10.1007/s10620-013-2735-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Accepted: 05/29/2013] [Indexed: 12/16/2022]
Abstract
BACKGROUND Perifosine, an alkylphospholipid, is an Akt inhibitor which inhibits the growth of diverse cancer cells. We have reported its inhibitory effects on the growth of gastric cancer cells recently, but its molecular mechanisms are still largely unknown. AIMS The purpose of this study was to investigate the effect and regulatory mechanism of perifosine in gastric cancer. METHODS Cell viability was determined by sulforhodamine B assay after transiently transfected with AEG-1 specific siRNAs. qRT-PCR and western blot assay were used to determine the mRNA expression and proteins levels of cell signaling molecules examined. Immunohistochemistry was used to detect the AEG-1 expression in 87 gastric carcinomas, 60 dysplasia, and 47 normal gastric mucosa. RESULTS Perifosine decreased AEG-1 gene expression along with inhibition of Akt/GSK3β/C-MYC signaling pathway. Knockdown of AEG-1 using siRNA led to significant down-regulation of cyclin D1 expression at both mRNA level and protein level, and inhibited the growth of gastric cancer cells. AEG-1 expression was elevated in gastric dysplasia and cancer tissues compared to normal gastric mucosa (P < 0.01). AEG-1 over-expression correlated with diffuse type of gastric cancer and advanced tumor stages. CONCLUSIONS Perifosine inhibits the growth of gastric cancer cells possibly through inhibition of the Akt/GSK3β/C-MYC signaling pathway-mediated down-regulation of AEG-1 that subsequently down-regulated cyclin D1. AEG-1 may play an important role in the carcinogenesis and progression of gastric cancer and could be a therapeutic target of perifosine.
Collapse
Affiliation(s)
- Wenbin Huang
- Department of Pathology, Nanjing Medical University Affiliated Nanjing Hospital (Nanjing First Hospital), Nanjing, 210006, Jiangsu, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Batista TP, de Mendonça LM, Fassizoli-Fonte AL. The role of perioperative radiotherapy in gastric cancer. Oncol Rev 2012; 6:e23. [PMID: 25992221 PMCID: PMC4419630 DOI: 10.4081/oncol.2012.e23] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 12/03/2012] [Accepted: 12/06/2012] [Indexed: 02/08/2023] Open
Abstract
Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide. Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease. However, despite the fact that surgery alone usually leads to favorable outcomes in early stage disease, late diagnosis usually means a poor prognosis. In these settings, multimodal therapy has become the established treatment for locally advanced tumors, while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy. We provide a critical, non-systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment.
Collapse
Affiliation(s)
| | - Lucas Marques de Mendonça
- Department of Radiotherapy, FPS/IMIP - Faculdade Pernambucana de Saúde, Instituto de Medicina Integral Professor Fernando Figueira, Recife/PE, Brazil
| | - Ana Luiza Fassizoli-Fonte
- Department of Radiotherapy, FPS/IMIP - Faculdade Pernambucana de Saúde, Instituto de Medicina Integral Professor Fernando Figueira, Recife/PE, Brazil
| |
Collapse
|
|
10
|
MicroRNA-27a inhibitors alone or in combination with perifosine suppress the growth of gastric cancer cells. Mol Med Rep 2012; 7:642-8. [PMID: 23175237 DOI: 10.3892/mmr.2012.1191] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Accepted: 11/12/2012] [Indexed: 01/11/2023] Open
Abstract
MicroRNA-27a (miR‑27a) is an oncogene that contributes to drug resistance in various types of cancer. However, the involvement of miR‑27a in gastric cancer has yet to be elucidated. Perifosine is an alkylphospholipid exhibiting antitumor activity as shown in both preclinical studies and clinical trials. The effects of perifosine on gastric cancer have yet to be determined. Therefore, this study was conducted to detect the role of miR‑27a and perifosine in human gastric cancer. miR‑27a was found to be expressed in human gastric cancer tissues and cell lines by quantitative reverse-transcription polymerase chain reaction (qRT‑PCR). The correlation between miR‑27a expression and clinicopathological characteristics of gastric cancer. We also explored the growth inhibitory effect of perifosine on human gastric cancer cells with or without co‑targeting miR‑27a by sulforhodamine B (SRB) assay. The results showed that miR‑27a expression was significantly upregulated in gastric cancer tissues, compared with their non‑tumor adjacent tissues. High expression levels of miR‑27a were associated with poor tumor histological grade (P=0.037). MiR‑27a inhibitors suppressed the growth of MGC‑803 cells. Assay results showed that perifosine exerted its activity selectively on the AGS cell line and the growth inhibitory effect of perifosine was enhanced significantly in combination with miR‑27a inhibitors in MGC‑803 cells. In conclusion, our results demonstrated that miR‑27a may be a therapeutic target and potential prognostic biological marker in gastric cancer. MiR‑27a inhibitors alone or in combination with perifosine may be a novel therapeutic approach against gastric cancer.
Collapse
|
|
11
|
Cardoso R, Coburn N, Seevaratnam R, Sutradhar R, Lourenco LG, Mahar A, Law C, Yong E, Tinmouth J. A systematic review and meta-analysis of the utility of EUS for preoperative staging for gastric cancer. Gastric Cancer 2012; 15 Suppl 1:S19-26. [PMID: 22237654 DOI: 10.1007/s10120-011-0115-4] [Citation(s) in RCA: 109] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 10/31/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND Accurate preoperative staging is important in determining the appropriate treatment of gastric cancer. Recently, endoscopic ultrasound (EUS) has been introduced as a staging modality. However, reported test characteristics for EUS in gastric cancer vary. Our purpose in this study was to identify, synthesize, and evaluate findings from all articles on the performance of EUS in the preoperative staging of gastric cancer. METHODS Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 1 December 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Meta-analysis for the performance of EUS was analyzed by calculating agreement (Kappa statistic), and pooled estimates of accuracy, sensitivity, and specificity for all EUS examinations, using histopathology as the reference standard. Subgroup analyses were also performed. RESULTS Twenty-two articles met our inclusion criteria and were included in the review. EUS pooled accuracy for T staging was 75% with a moderate Kappa (0.52). EUS was most accurate for T3 disease, followed by T4, T1, and T2. EUS pooled accuracy for N staging was 64%, sensitivity was 74%, and specificity was 80%. There was significant heterogeneity between the included studies. Subgroup analyses found that annual EUS volume was not associated with EUS T and N staging accuracy (P = 0.836, 0.99, respectively). CONCLUSION EUS is a moderately accurate technique that seems to describe advanced T stage (T3 and T4) better than N or less advanced T stage. Stratifying by EUS annual volume did not affect EUS performance in staging gastric cancer.
Collapse
Affiliation(s)
- Roberta Cardoso
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada
| | | | | | | | | | | | | | | | | |
Collapse
|
|
12
|
Shi L, Zhou Q, Wu J, Ji M, Li G, Jiang J, Wu C. Efficacy of adjuvant immunotherapy with cytokine-induced killer cells in patients with locally advanced gastric cancer. Cancer Immunol Immunother 2012; 61:2251-9. [PMID: 22674056 PMCID: PMC3506195 DOI: 10.1007/s00262-012-1289-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 05/18/2012] [Indexed: 12/15/2022]
Abstract
Purpose To determine the long-term efficacy of adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells for locally advanced gastric cancer patients. Experimental design One hundred and fifty-one patients with stage III/IV gastric cancer who had undergone gastrectomy were enrolled, assigned to two groups (immunotherapy group versus no immunotherapy group/or control group), and followed. Results The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates for immunotherapy versus control group were 32.4 versus 23.4 % (P = 0.071) and 28.3 versus 10.4 % (P = 0.044), respectively. For patients with intestinal-type tumors, the 5-year OS and DFS rates were significantly higher for immunotherapy (OS, 46.8 vs. 31.4 % and P = 0.045; DFS, 42.4 vs. 15.7 % and P = 0.023). In the immunotherapy group, the mean CD3+ level, CD4+ level, and CD4+/CD8+ ratio increased from 50.8, 26.5, and 0.9 %, respectively, at baseline to 62.6, 35.0, and 1.4 %, respectively, 1 week after the first CIK-cell treatment, returned to baseline after 2 months, and maintained a higher level (60.7 ± 8.2 %, 34.2 ± 7.1 %, and 1.3 ± 0.3 %, respectively) 2 months after 3 cycles of immunotherapy. Conclusions Adjuvant immunotherapy with CIK cells prolongs DFS in patients with locally advanced gastric cancer and significantly improves OS in patients with intestinal-type tumors. Intestinal-type tumors could be selected as an important indication for CIK-cell therapy. This treatment may help improve T-lymphocyte subset distribution and improve the host’s immune functions, but multiple cycles are necessary for long-term therapeutic efficacy.
Collapse
Affiliation(s)
- Liangrong Shi
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China
| | | | | | | | | | | | | |
Collapse
|
|
13
|
Shulman K, Haim N, Wollner M, Bernstein Z, Abdah-Bortnyak R, Bar-Sela G. Postoperative chemotherapy in gastric cancer, consisting of etoposide, doxorubicin and cisplatin, followed by radiotherapy with concomitant cisplatin: A feasibility study. Oncol Lett 2012; 3:1154-1158. [PMID: 22783410 DOI: 10.3892/ol.2012.617] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Accepted: 02/06/2012] [Indexed: 02/07/2023] Open
Abstract
The prognosis following surgical treatment of gastric carcinoma (GC) or gastroesophageal junction (GEJ) adenocarcinoma remains poor. Although adjuvant chemo-radiotherapy with 5-fluorouracil has been shown to be beneficial, a high rate of distant failure has been reported. Thus, the toxicity profile and efficacy of an intensified chemo-radiotherapy regimen following complete or near-complete resection of GC was evaluated. Patients who underwent surgery for GC were eligible for evaluation. Treatment consisted of four cycles of modified EAP: etoposide 100 mg/m(2), days 1-3; cisplatin 27 mg/m(2), days 1-3; and adriamycin 40 mg/m(2), day 1; every 21 days, followed by a course of radiotherapy (45 Gy; 1.8 Gy/fr) combined with weekly cisplatin 40 mg/m(2). In total, 40 patients were included in the analysis. Median follow-up was 34 months from the onset of chemotherapy. Microscopic stage IV disease and/or R1 resection were found in 11 patients. For these patients, the median progression-free survival was 6.5 months, and overall survival 9.5 months, compared to 25 and 54 months, respectively, for the remaining 29 patients. In the latter subgroup, longer disease-free survival was associated with average dose intensity of >90% for the four cycles of EAP. The predominant grade 3-4 toxicities during EAP-chemotherapy were hematological adverse events. Nevertheless, the rate of severe non-hematologic toxicity reached 60%. There was one toxicity-related mortality. During the chemo-radiotherapy course, 39% of patients experienced grade 3-4 non-hematologic toxicities. It was concluded that the high toxicity rate of this regimen does not justify further evaluation of this postoperative protocol. Chemo-radiotherapy for R1 or pathological microscopic M1 patients does not appear to be justified.
Collapse
Affiliation(s)
- Katerina Shulman
- Division of Oncology, Rambam Health Care Campus, and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
| | | | | | | | | | | |
Collapse
|
|
14
|
Li ZY, Koh CE, Bu ZD, Wu AW, Zhang LH, Wu XJ, Wu Q, Zong XL, Ren H, Tang L, Zhang XP, Li JY, Hu Y, Shen L, Ji JF. Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer. J Surg Oncol 2011; 105:793-9. [PMID: 22189752 DOI: 10.1002/jso.23009] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Accepted: 11/24/2011] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. METHODS This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan-Meier log rank test was used to calculate and compare survival differences. RESULTS There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1-2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths. CONCLUSION Peri-operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri-operative ECF.
Collapse
Affiliation(s)
- Zi-Yu Li
- Department of Gastrointestinal Surgery, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Van Cutsem E, Dicato M, Geva R, Arber N, Bang Y, Benson A, Cervantes A, Diaz-Rubio E, Ducreux M, Glynne-Jones R, Grothey A, Haller D, Haustermans K, Kerr D, Nordlinger B, Marshall J, Minsky BD, Kang YK, Labianca R, Lordick F, Ohtsu A, Pavlidis N, Roth A, Rougier P, Schmoll HJ, Sobrero A, Tabernero J, Van de Velde C, Zalcberg J. The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2010. Ann Oncol 2011; 22 Suppl 5:v1-v9. [PMID: 21633049 DOI: 10.1093/annonc/mdr284] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Well-recognized experts in the field of gastric cancer discussed during the 12th European Society Medical Oncology (ESMO)/World Congress Gastrointestinal Cancer (WCGIC) in Barcelona many important and controversial topics on the diagnosis and management of patients with gastric cancer. This article summarizes the recommendations and expert opinion on gastric cancer. It discusses and reflects on the regional differences in the incidence and care of gastric cancer, the definition of gastro-esophageal junction and its implication for treatment strategies and presents the latest recommendations in the staging and treatment of primary and metastatic gastric cancer. Recognition is given to the need for larger and well-designed clinical trials to answer many open questions.
Collapse
Affiliation(s)
- E Van Cutsem
- University Hospital Gasthuisberg, Leuven, Belgium.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|