Gastric cancer (cancer of the stomach) is a disease in which malignant cells arise in the tissues of the stomach. Early symptoms can include indigestion, feeling bloated after eating, mild nausea, loss of appetite, or heartburn. In more advanced stages symptoms may include blood in the stool, vomiting, weight loss, or pain in the stomach. Known risk factors include prior stomach infection by Helicobacter pylori, smoking, frequent diet of dry salted foods, Menetrier's disease, and familial polyposis. Most cancers of the stomach are adenocarcinomas of which there are many sub-types.
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AGA Founded in 1897, the AGA has grown to include more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. Gastrointestinal System Cancers
Gastric Breast Cancer Editorial Office Provides secondary-research articles (editorials, perspectives, news/views etc) on best practice and future clinical and research directions prevention and early detection, multidisciplinary, evidence-based management and treatment of breast cancer and gastric cancer. International editorial board, peer reviewed and open access. Breast Cancer
Springer "The multidisciplinary Journal of Gastrointestinal Cancer publishes novel research pertaining to cancers arising from the gastrointestinal tract. Coverage spans all relevant fields, emphasizing studies that aid in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus." Gastrointestinal System Cancers
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Hopper AD Early endoscopy improves survival in gastric cancer. Practitioner. 2014 Jul-Aug; 258(1773):23-7, 2 [PubMed] Related Publications
Gastric cancer often presents late and the mortality ratio remains one of the highest compared with more common cancers. Early diagnosis improves survival in this potentially curable cancer. Men are twice as likely as women to develop gastric cancer. The vast majority (96%) of cases occur in people above the age of 55. Dysphagia, weight loss and age over 55 are significant predictors of cancer. All patients presenting with dyspepsia and either alarm features or known conditions that increase the risk of gastric cancer should be referred for urgent endoscopy. Given that the majority of gastric 0032-6518 cancer cases occur in people over 55, urgent endoscopy is also recommended in this group with new uncomplicated dyspepsia prior to treatment, even without alarm symptoms or if the symptoms respond to treatment. Upper GI endoscopy with biopsy is the recommended investigation to confirm gastric cancer. Patients deemed medically fit should undergo surgical resection to cure early gastric cancer and chemotherapy followed by surgical resection for higher stage tumours. More than half of all patients with gastric cancer present with incurable advanced disease; palliative chemotherapy has a small but significant effect on survival.
Jeon CH, Kim IH, Chae HD Prognostic value of genetic detection using CEA and MAGE in peritoneal washes with gastric carcinoma after curative resection: result of a 3-year follow-up. Medicine (Baltimore). 2014; 93(11):e83 [PubMed] Related Publications
Peritoneal metastasis is the most frequent cause of death in patients with gastric cancer. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay of peritoneal washes has been used to predict peritoneal metastasis of gastric carcinoma. We applied carcinoembryonic antigen (CEA) and melanoma-associated gene (MAGE) RT-PCR for the detection of peritoneal metastasis of gastric carcinoma after curative surgery and evaluated its clinical significance. Peritoneal washes were obtained from 117 patients with gastric carcinoma. MAGE A1-A6 and CEA RT-PCR were performed, and the results were evaluated according to their clinicopathologic characteristics. Three-year follow-up clinical studies were periodically performed, and disease-free survival rates were retrospectively investigated using the medical records. Among 117 peritoneal fluids, 11 cases (9.4%) revealed MAGE expression and 38 cases (32.5%) revealed CEA expression. When focusing on recurrence rates, RT-PCR-positive had much higher recurrence rates than RT-PCR-negative cases (32.5% vs 5.2%, P < 0.01). Univariate analysis revealed that depth of invasion, lymph node metastasis, tumor node metastasis (TNM) stage, Lauren classification, and MAGE and CEA expressions were independent prognostic factors for recurrence. In a multivariate analysis, MAGE expression and TNM stage were significantly and independently related to recurrence in patients who underwent curative resection. MAGE expression was determined to be the most important prognostic factor for recurrence (hazard ratio: 12.487, P < 0.01). It is feasible to identify free cancer cells in peritoneal lavage by using a MAGE A1-A6 and CEA RT-PCR. MAGE RT-PCR results disclosed significant associations with peritoneal recurrence and proved to be the most important factor for the recurrence rate in patients with gastric carcinoma who had undergone radical resection.
Zhang F, Tang JM, Wang L, et al. Immunohistochemical detection of RET proto-oncogene product in tumoral and nontumoral mucosae of gastric cancer. Anal Quant Cytopathol Histpathol. 2014; 36(3):128-36 [PubMed] Related Publications
OBJECTIVE: To detect RET (REarranged during Transfection) protein by immunohistochemistry (IHC) in gastric cancer. STUDY DESIGN: A total of 210 samples were employed, of which 197 specimens were from 91 surgical pieces of gastric adenocarcinoma, comprising 91 tumoral, 91 nontumoral, and 15 intramucosal dysplastic samples. Another 13 gastric mucosae were from cancer-free patients. Two RET antibodies (clones Ret01 and 3F8) were used separately for IHC. RESULTS: Of the nontumoral samples from gastric cancers, 28 were positive (31%) with either antibody Ret01 or 3F8. The positive stains were often located in deep pyloric glands and associated with chronic inflammation patterns (p = 0.045). RET positivity correlated with phosphorylated epidermal growth factor receptor, which had been previously tested (p = 0.021). In tumoral samples RET was positive in 7 cases with antibody Ret01 (8%) and 9 cases with 3F8 (10%). In 15 intramucosal dysplastic samples RET was detected in 6 cases with antibody Ret01 and 8 cases with 3F8. There was an accordance between the IHC using antibodies Ret01 and 3F8 in tumoral, nontumoral, and intramucosal dysplastic samples (p = 0.500, 1.000, and 0.500). The 13 samples from cancer-free patients were always negative. CONCLUSION: Activation of RET proto-oncogene may be one of the molecular pathogeneses in gastric inflammatory and tumoral diseases.
Sandler S Esophagogastric junction and gastric adenocarcinoma: neoadjuvant and adjuvant therapy, and future directions. Oncology (Williston Park). 2014; 28(6):505-12 [PubMed] Related Publications
In North America, gastric cancer is the third most common gastrointestinal malignancy and the third most lethal neoplasm overall. In Asia, gastric cancer represents an even more serious problem: in Japan, it is the most common cancer in men. The standard primary therapy for gastric cancer is surgical resection; in esophagogastric-junction (EGJ) adenocarcinoma, which is often included in studies of gastric cancer, surgery is also typically the initial management strategy. However, the rates of locoregional and distant recurrence following surgery with curative intent have remained high. Investigators have explored a variety of ways of reducing these rates and improving survival in patients with gastric and EGJ cancers. These strategies have included explorations of the optimal extent of regional lymphadenectomy at the time of gastric resection; investigation of different neoadjuvant, perioperative, and adjuvant chemotherapy regimens; use of preoperative and postoperative radiation therapy; and the use of pre- and postoperative chemoradiotherapy (CRT).To date, benefit has been seen in gastric cancer patients with the use of what is called a"D2 resection"(which includes lymph nodes of stations 7 through 12) and with adjuvant CRT (in the West) or adjuvant chemotherapy with S-1 (in Japan); and neoadjuvant CRT has been shown to have a survival benefit in patients with EGJ cancers.
Gryko M, Kiśluk J, Cepowicz D, et al. Expression of insulin-like growth factor receptor type 1 correlate with lymphatic metastases in human gastric cancer. Pol J Pathol. 2014; 65(2):135-40 [PubMed] Related Publications
Most patients with gastric cancer are diagnosed at advanced clinical stages with a high frequency of lymph node metastasis. It is very important to find novel factors for the early diagnostic and prognostic evaluation of gastric cancer. It has been shown that IGF-1R activates mitotic division and inhibits apoptosis of cancer cells through the activation of signaling MAP/ERK and PI3K/Akt-1 pathways. IGF-1R plays a role in cell transformation and maintenance of the phenotype in modified cells. Moreover, an IGF-1 receptor effect influences the processes of adhesion, migration, invasion and metastasis of tumor cells. The aim of the study was to assess the expression of IGF-1R in gastric carcinoma in correlation with selected anatomo-clinical parameters. The study enrolled a group of 49 patients treated surgically for gastric cancer. 28 patients had no lymph node metastases. The expression of the studied proteins was assessed using the immunohistochemical method. We found that the expression of IGF-1R in gastric cancer is associated with lymph node metastasis (p < 0.001), is correlated with worse prognosis and high histological malignancy grade, and is an independent predictor of survival in patients with gastric cancer (p < 0.001). IGF-1R may play an important role in tumor growth and metastasis via the lymphatic pathway.
Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.
Minoda Y, Akahoshi K, Oya M, et al. Gastric glomus tumor diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: report of a case. Fukuoka Igaku Zasshi. 2014; 105(4):105-9 [PubMed] Related Publications
A glomus tumor of the stomach is rare. It is difficult to diagnose the tumor before surgery by only endoscopic biopsy and radiography, and there is no established method of diagnosis before surgical treatment. Esophagogastroduodenoscopy (EGD) on a 50-year-old Japanese woman revealed a 10 mm submucosal tumor in the anterior wall of the gastric angle. Follow-up EGD revealed an increase in the size of the tumor to 15mm. Endoscopic ultrasonography (EUS) demonstrated a 15mm subepithelial hypoechoic solid tumor with continuity to the proper muscle layer. Histologic diagnosis by endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) was glomus tumor. The tumor was treated by laparoscopic local resection. The histologic diagnosis of the resected tumor was similar to the preoperative EUS-FNA results. EUS-FNA would appear to be an effective histologic test for early diagnosis of gastric glomus tumor.
Cheng Y, Li Y, Liu D, et al. miR-137 effects on gastric carcinogenesis are mediated by targeting Cox-2-activated PI3K/AKT signaling pathway. FEBS Lett. 2014; 588(17):3274-81 [PubMed] Related Publications
The discovery of microRNAs (miRNAs) provided a new avenue for early diagnosis and treatment of GC. MiR-137 has been reported to be under-expressed and involved in various cell processes. However, the role of miR-137 in GC is less known. In this study, we show that miR-137 is under-expressed in GC and functions as a tumor suppressor through targeting Cyclooxygenase-2 (Cox-2), which subsequently suppresses the activation of PI3K/AKT signaling pathway both in vitro and in vivo. Moreover, restored Cox-2 expression partially abolished the tumor suppressive effects of miR-137 in GC cells, suggesting miR-137 may suppress GC carcinogenesis by targeting Cox-2.
Lee NK, Lee JH, Park CH, et al. Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma. Biochem Biophys Res Commun. 2014; 451(2):171-8 [PubMed] Related Publications
Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastric cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.
Li Y, Du P, Zhou Y, et al. Lymph node micrometastases is a poor prognostic factor for patients in pN0 gastric cancer: a meta-analysis of observational studies. J Surg Res. 2014; 191(2):413-22 [PubMed] Related Publications
BACKGROUND: There is no consensus as to the impact of lymph node micrometastases (LNMM) on survival of patients with gastric cancer. The aim of this analysis was to investigate the prognostic significance of LNMM in patients with histologic node-negative gastric cancer. METHODS: We searched relevant studies from PubMed, Embase, and the Cochrane Library (1966-2013.5), used software STATA 12.0 to pool the outcomes of each study. Mantel-Haenszel and Inverse Variance methods were used in a fixed effect model and a random effect model, respectively. The hazard ratios (HR) and odds risk (OR) at their 95% confidence intervals (CIs) were used as measures to investigate the prognostic importance of LNMM, by searching for a correlation between the clinical pathologic features and LNMM. RESULTS: Our analysis of 18 eligible studies revealed that patients with LNMM had an increased likelihood of having a worse 5-y survival rate (HR 2.81; 95% CI: 1.96-4.02). Subgroup analyses showed a more significant result for patients in pT1-2N0 (HR 3.52; 95% CI 1.88-6.62). The analyses also revealed that (OR 1.32; 95% CI 1.17-1.48), lymphatic invasion (OR 2.21; 95% CI 1.42-3.44) and venous invasion (OR 1.41; 95% CI 1.08-1.85) were associated with the occurrence of LNMM. CONCLUSIONS: There is a positive correlation between LNMM and an unfavorable surgical outcome in gastric cancer. Undifferentiated histologic findings, lymphatic invasion, and venous invasion are high risk factors for the occurrence of LNMM.
Yu J, Deng Y, Chen JP N-acetyltransferase 2 status and gastric cancer risk: a meta-analysis. Tumour Biol. 2014; 35(7):6861-5 [PubMed] Related Publications
Case-control studies on the association between N-acetyltransferase 2 (NAT2) genotype and gastric cancer have provided either controversial or inconclusive results. In order to clarify the influence of NAT2 acetylation status on gastric cancer risk, a meta-analysis was undertaken. The primary outcome measure was the odds ratio (OR) for the risk of gastric cancer associated with the NAT2 genotype. The overall result showed that there was no statistically significant association between NAT2 status and gastric cancer risk (slow acetylation vs. rapid acetylation, OR = 1.10, 95 % confidence interval (CI) 0.97-1.25, p = 0.12). In the analysis stratified by East Asian ethnicity, a significant association was found between gastric cancer and the NAT2 genotype (slow acetylation vs. rapid acetylation, OR = 1.33, 95 % CI 1.11-1.59, p = 0.002). Our pooled data suggest that the NAT2 acetylation status has an effect on the risk of gastric cancer among East Asian populations.
Deshpande G, Samarasam I, Chandran BS, et al. Extended multiorgan resection in locally advanced gastric cancer: a single centre experience from south India. Trop Gastroenterol. 2013 Oct-Dec; 34(4):259-63 [PubMed] Related Publications
BACKGROUND: The prognostic and survival benefit of extended multiorgan resection for locally advanced gastric adenocarcinoma remains controversial. The morbidity associated with additional organ resection has been found to be higher when compared to patients undergoing gastrectomy alone. The aim of our study was to evaluate the morbidity, mortality and survival benefit associated with extended multiorgan resection for locally advanced gastric adenocarcinoma. METHODS: From January 2004 to December 2011, 721 patients underwent resectional surgery for gastric adenocarcinoma at the Christian Medical College, Vellore, India. Out of this group, 36 patients underwent primary resection and had one or more organs resected in addition to the stomach. A retrospective analysis of the case records of all these patients was performed. The Kaplan-Meier survival probability was estimated. Cox regression analysis was used to evaluate the clinico-pathological variables affecting the survival of these patients. RESULTS: The perioperative morbidity and mortality rates were 25% and 5.5% respectively. The most common organs resected were colon and spleen. The incidence of pathologically confirmed T4b cancers was only 50%. The median survival of these patients was 28 months. The survival was influenced by a R0 or curative resection. However, it was not statistically significant. CONCLUSION: Extended multiorganresection in locally advanced gastric cancer can be performed with acceptable morbidity and mortality. In our study, overstaging was found in 50% of the patients and hence, when the real nature of invasion is unclear, the surgeon may proceed with en bloc resection of the stomach with the involved adjacent organs. As long as an R0 resection can be achieved, extended multiorgan resection can be performed for carcinoma stomach.
Rudloff U, Langan RC, Mullinax JE, et al. Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial. J Surg Oncol. 2014; 110(3):275-84 [PubMed] Related Publications
BACKGROUND: A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis. METHODS: Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum, and resectable to "no evidence of disease" were randomized to gastrectomy, metastasectomy, HIPEC, and systemic FOLFOXIRI (GYMS arm) or FOLFOXIRI alone (SA arm). RESULTS: Seventeen patients were enrolled (16 evaluable); 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction (CCR0). Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm. Four patients in the GYMS arm survived >12 months, 2 patients close to 2 years at last follow-up, and 1 patient more than 4 years, with 2 of these patients still alive. No patient in the SA arm lived beyond 11 months. All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index (PCI) of ≤ 15. CONCLUSION: Maximal cytoreductive surgery combined with regional (HIPEC) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival.
Zheng Y, Fang W, Mao C, et al. Biweekly S-1 plus paclitaxel (SPA) as second-line chemotherapy after failure from fluoropyrimidine and platinum in advanced gastric cancer: a phase II study. Cancer Chemother Pharmacol. 2014; 74(3):503-9 [PubMed] Related Publications
PURPOSE: Second-line chemotherapy is now considered a standard therapy option in patients with advanced gastric cancer (AGC) who failed from first-line chemotherapy. Single agents, such as irinotecan, docetaxel or paclitaxel, provided an overall response rate of about 10 %. However, the efficacy was not satisfactory. The authors conducted a phase II study to investigate biweekly regimen of S-1 plus paclitaxel in Chinese AGC in second-line setting, with response rate as the primary end point. PATIENTS AND METHODS: Patients with AGC failed from first-line chemotherapy with fluoropyrimidine/platinum who had measurable lesions were enrolled. Paclitaxel was administered intravenously on day 1 at a dose of 120 mg/m(2), and oral S-1 was administered twice a day from days 1 to 7, followed by a 7-day drug-free interval. RESULTS: A total of 30 patients with pretreated AGC were accrued. No complete responses were observed. Partial responses were documented in 10 (33.3 %) patients. Ten (33.3 %) patients had stable disease. The median progression-free survival was 3.6 months and the overall survival was 7.2 months. The main toxicity was bone marrow suppression. The most frequent grade 3/4 hematological toxicities were neutropenia and anemia, which were observed in 8 (26.7 %) and 6 (20 %) patients, respectively. The most common grade 3/4 non-hematological toxicity was neuropathy, which was reported in 4 (13.3 %) patients. CONCLUSION: Biweekly S-1 plus paclitaxel showed promising activity with acceptable toxicities as second-line chemotherapy in pretreated patients with AGC. This regimen deserves further investigation in a phase III trial.
The diffuse-type histologic variant of gastric cancer is characterized by highly invasive growth patterns and lack of cellular cohesion. Two recent studies have identified highly recurrent mutations of the gene encoding the small GTPase RhoA and suggest that RhoA activity may have a tumor suppressive role in this disease.
Liu T, Sun Y, Wang Y Gastric cancer with para-aortic lymph nodes metastasis: curable dissection possible but be cautiously selected. Cancer Chemother Pharmacol. 2014; 74(2):435-6 [PubMed] Related Publications
This is a reply letter to Dr. M Daniele et al. entitled as "gastric cancer with para-aortic lymph nodes metastasis: do not miss a chance of cure!". Para-aortic lymph node metastasis has been regarded as a pattern of distant metastasis in gastric cancer. Even patients with PAN metastasis undergo extensive lymph nodes, the prognosis is unsatisfactory and the overall survival is not better than the patients receiving palliative chemotherapy. However, for the patients who were responded to the preoperative chemotherapy, subsequent radical gastrectomy performed prolonged survival. Meanwhile, patients who were resistant to the previous chemotherapy were not optimal candidates for curative resection in advanced gastric cancer patients with PAN metastasis. How large with lymph nodes dissection for the patients with initially PAN metastasis after effective neo-chemotherapy is still a controversial issue and needs further large-scale randomized trials.
Li B, Rao N, Liu D, et al. Analysis of connection networks among miRNAs differentially expressed in early gastric cancer for disclosing some biological features of disease development. Gene. 2014; 548(2):159-65 [PubMed] Related Publications
This paper first identified differentially expressed miRNAs associated with early gastric cancer and then respectively constructed relevant connection networks among the identified differentially expressed miRNAs that corresponded to early gastric cancer and control tissues. Twenty-three differentially expressed miRNAs were identified, 18 of which were different with the related results on the same data, and they provide great discriminatory power between patients and controls. There are not only conserved unchangeable sub-networks but also different sub-networks between the two connection networks. From the consistency and differences between two connection networks, we disclosed several new biological features that promote early gastric cancer development. This study shows 23 miRNAs that are early gastric cancer-specific and are worthy to do further experimental studies. The revealed biological features for early gastric cancer will provide new insights into improved understanding of the molecular mechanisms of this disease.
Shen YC, Li CP, Yen CJ, et al. Phase II multicentered study of low-dose everolimus plus cisplatin and weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin as first-line treatment for patients with advanced gastric cancer. Oncology. 2014; 87(2):104-13 [PubMed] Related Publications
OBJECTIVE: This phase II trial investigates the efficacy and safety of low-dose everolimus in combination with cisplatin-fluorouracil chemotherapy in patients with advanced gastric cancer. METHODS: Eligible patients with chemotherapy-naïve advanced gastric cancer received low-dose everolimus (10 mg p.o. on days 1, 8 and 15) plus cisplatin and a weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (HDFL) chemotherapy (cisplatin 35 mg/m(2) intravenous infusion for 24 h on days 1 and 8, 5-fluorouracil 2,000 mg/m(2) and leucovorin 300 mg/m(2) intravenous infusion for 24 h on days 1, 8 and 15) every 28 days. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.0. RESULTS: Forty patients (19 men; 21 women; median age, 54.1 years; range, 33.7-73.3 years) received a median of 6 (range, 1-30; 95% CI, 4.9-8.0) cycles of study treatment. The ORR was 52.5% (21 confirmed partial response). The median progression-free survival and overall survival were 6.9 (95% CI, 4.9-8.4) and 10.5 (95% CI, 8.6-12.3) months, respectively. Most adverse events were mild. CONCLUSION: Adding low-dose everolimus to cisplatin-HDFL chemotherapy failed to increase the ORR as in a preplanned statistical assumption but may prolong progression-free survival in treatment-naïve advanced gastric cancer patients.
Liu X, Liu Q, Fan Y, et al. Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells. FEBS Lett. 2014; 588(17):3160-9 [PubMed] Related Publications
PPP2R5E belongs to the phosphatase 2A regulatory subunit B family and acts as a tumor suppressor in human cancer. However, the role of PPP2R5E in the tumorigenesis of gastric cancer is unclear. Here, we declare that PPP2R5E is downregulated by miR-23a and induces cell growth inhibition and apoptosis in gastric cancer cells. Furthermore, ASO-miR-23a suppresses tumor growth derived from MGC803 cells in vivo. PPP2R5E is identified as a new target of miR-23a. Moreover, overexpression of PPP2R5E reversed the negative effects of miR-23a. We highlight the significance of miR-23a and PPP2R5E in the proliferation and apoptosis of gastric cancer cells.
Chen WL, Shen CL, Chang YM, et al. Pulmonary metastatic gastric cancer mimicking a giant mediastinal cyst. Ann Thorac Surg. 2014; 98(1):329-31 [PubMed] Related Publications
Cysts and cavities are common radiologic abnormalities. Pulmonary metastasis comprises a rare entity of thoracic cystic diseases. We reported a case of giant cyst at the left anterior mediastinum that was pathologically confirmed as a lung metastasis from previously resected gastric cancer. The cyst was completely removed with wedge resection of the surrounding lung through a left anterior thoracotomy. One should always keep in mind the possibility of an intrathoracic cyst near or at the mediastinal region that may originate from metastatic lesions to the lungs when patients have previous cancer history.
Li Y, Liu Z, Liu H, et al. Potentially functional variants in the core nucleotide excision repair genes predict survival in Japanese gastric cancer patients. Carcinogenesis. 2014; 35(9):2031-8 [PubMed] Related Publications
Functional genetic variants of DNA repair genes may alter the host DNA repair capacity, and thus influence efficiency of therapies. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in genes (i.e. ERCC1, XPA, XPC, XPD and XPG) involved in the nucleotide excision repair (NER) pathway in 496 Japanese gastric cancer patients, and assessed overall survival and recurrence-free survival. The combined effects of risk genotypes of these eight SNPs in Japanese patients were further replicated in 356 North-American gastric cancer patients. In Japanese patients, we found that the XPC rs2228000 TT genotype was associated with shorter overall survival [hazards ratio (HR) = 1.75, 95% confidence interval (95% CI) = 1.07-2.86] and recurrence-free survival (HR = 2.17, 95% CI = 1.19-3.95), compared with CC/CT genotypes, and the XPG rs17655 CC genotype was associated with shorter overall survival (HR = 1.60, 95% CI = 1.08-2.36), compared with GG/CG genotypes. The number of observed risk genotypes in the combined analysis was associated with shorter overall survival and recurrence-free survival in a dose-response manner (P(trend) = 0.006 and P(trend) < 0.000) in Japanese patients; specifically, compared with those with ≤1 risk genotypes, those with ≥2 risk genotypes showed markedly shorter overall survival (HR = 1.79, 95% CI = 1.18-2.70) and recurrence-free survival (HR = 2.80, 95% CI = 1.66-4.73). The association between ≥2 risk genotypes and shorter overall survival was not significant (HR = 1.26, 95% CI = 0.82-1.94) in North-American patients, but the trends were similar in these two groups of patients. These data show that functional SNPs in NER core genes may impact survival in Japanese gastric cancer patients.
Kim J, Jang SG, Kwon SY, et al. MicroRNA signature for HER2-positive breast and gastric cancer. Anticancer Res. 2014; 34(7):3807-10 [PubMed] Related Publications
BACKGROUND/AIM: The molecular mechanism for aggressive clinical behaviour related to v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) amplification is not fully-understood. In particular, little is known about microRNAs in the human epidermal growth factor receptor 2 (HER2) signaling network. PATIENTS AND METHODS: Using microRNA microarray, the microRNA profiles of 16 HER2-positive breast carcinomas were compared with those of five luminal-type breast carcinomas. Additionally, two frozen, ERBB2-amplified gastric carcinomas were compared with their adjacent normal tissue samples. MicroRNAs that were differentially expressed according to the HER2 status in breast and gastric carcinomas were identified as the HER2 microRNA signature. RESULTS: MiR-337 and miR-302f were commonly overexpressed in HER2-postive breast and gastric cancer. MiR-139 and miR-129 were commonly underexpressed in HER2-positive breast and gastric cancer. A concordant pattern of microRNA expression was noted between discovery sets and the majority of candidate microRNAs (two out of three) in three validation sets. CONCLUSION: Our study identified novel microRNAs that were differentially expressed according to the HER2 status across different tumor types.
Kuo HY, Yeh KH Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review. Anticancer Res. 2014; 34(7):3695-9 [PubMed] Related Publications
The prognosis of advanced gastric cancer (AGC) remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. However, malnutrition and poor performance of AGC in late stages usually preclude such patients from intensive treatment. Many targeted-therapies failed to show a significant survival benefit in AGC, but have regained attention after the positive result of ramucirumab was announced last year. Among all targeted agents, only trastuzumab, a monoclonal antibody against Human epidermal growth factor receptor-2 (HER2) protein, has been proven as having survival benefit by addition to first-line chemotherapy. Herein we reported a patient who benefited from adding trastuzumab to the same second-line combination chemotherapy (paclitaxel, 5-fluorouracil, and leucovorin) upon progression of bulky liver metastases. At least five months of progression-free survival were achieved without any additional toxicity. We also reviewed literature of molecularly-targeted therapy for chemotherapy-refractory gastric cancer, including several large phase III trials (REGARD, GRANITE-1, EXPAND, and REAL-3) published in 2013-2014.
Gonzalez-Hormazabal P, Musleh M, Bustamante M, et al. Role of cytokine gene polymorphisms in gastric cancer risk in Chile. Anticancer Res. 2014; 34(7):3523-30 [PubMed] Related Publications
AIM: To assess the role of pro- and anti-inflammatory polymorphisms in gastric cancer susceptibility. PATIENTS AND METHODS: We genotyped 12 polymorphisms in eight cytokine genes (Interleukin-1β -IL1B-, IL8, IL17A, IL17F, IL32, tumor necrosis factor-α -TNF-, IL1RN, IL10) in a case-control study of 147 patients with gastric cancer and 172 controls. RESULTS: Single polymorphism analysis revealed an association between the IL10 -592C>A single nucleotide polymorphism and cases with moderately- or well-differentiated tumors [AA vs. GG, odds ratio (OR)=3.01; 95% confidence interval (CI)=1.08-8.50]. We further analyzed gene-gene interactions using a combined attribute network implemented in multifactor dimensionality reduction software. The analysis revealed an interaction between IL8 -251A>T and IL32 rs28372698 SNPs among cases with moderately- or well-differentiated tumors. Homozygosity for both IL8 -251T and IL32 T alleles increases the odds for developing gastric cancer up to 2.63-fold (OR=2.63; 95% CI=1.15-6.03). This association was higher compared to the homozygosity for the IL8-251 T allele alone (OR=1.11; 95% CI=0.51-2.43) or the IL32 T allele alone (OR=1.21; 95% CI=0.54-2.72). CONCLUSION: These findings suggest that IL10 -592C>A increases the odds for developing gastric cancer. An interaction between IL8 -251A>T and IL32 rs28372698 SNPs is also proposed.
Taban O, Cimpean AM, Raica M, Olariu S PROX1 expression in gastric cancer: from hypothesis to evidence. Anticancer Res. 2014; 34(7):3439-46 [PubMed] Related Publications
BACKGROUND: PROX1 is involved in cancer development and progression as both a tumor suppressor and oncogene. Immunohistochemical (IHC) PROX1 nuclear expression is a widely accepted pattern. Scattered data reported PROX1 IHC cytoplasmic expression in different tumors, including gastric cancer but it is not clear if this holds true. MATERIALS AND METHODS: Evaluation of the cytoplasmic expression of PROX1 in normal gastric mucosa and gastric cancer was performed by IHC followed by RNAscope, an in situ hybridization-based method for detecting PROX1 mRNA amplification on paraffin-embedded samples and to evaluate its clinical impact. RESULTS: Twenty five out of 48 cases of gastric cancer showed PROX1 nuclear and cytoplasmic immunohistochemical expression. Twelve out of these 20 cases positive for PROX1 on IHC (54.5%) had PROX1 mRNA gene amplification. The overlapping of PROX1 cytoplasmic expression assessed by immunohistochemistry and cytoplasmic RNAscope amplification was statistically significant (p=0.031). PROX1 mRNA gene amplification correlated with tumor grade (p=0.05) and regional lymph node metastasis as well (p=0.033). No significant correlation was obtained between PROX1 and histopathology, tumor size or distal metastasis. CONCLUSION: A significant correlation was found between IHC and RNAscope PROX1 expression in the cytoplasm of normal and gastric cancer cells. This strongly supports its validation as a true expression on immunohistochemistry. A strong correlation between PROX1 mRNA amplification and regional lymph node metastasis supports its implications in cancer spreading and metastasis and sustains its utility, not only as a lymphatic marker, but also as a potential tumor marker in various tumor types, including gastric cancer.
Kawamura M, Tanaka K, Toiyama Y, et al. Clinical significance of tartrate-resistant acid phosphatase type-5 expression in human gastric cancer. Anticancer Res. 2014; 34(7):3425-9 [PubMed] Related Publications
AIM: The present study investigated the clinical significance of tartrate-resistant acid phosphatase type-5 (ACP5) expression in gastric cancer. MATERIALS AND METHODS: In 150 specimens of gastric cancer and adjacent normal mucosa, expression of ACP5 protein and mRNA and was determined by immunohistochemical staining and quantitative real-time polymerase chain reaction, respectively. RESULTS: Expression of ACP5 mRNA was significantly higher in cancer tissues than in adjacent normal mucosa. Elevated ACP5 mRNA was associated with lymph node metastasis and peritoneal dissemination. Logistic regression analysis revealed that elevated ACP5 expression was an independent risk factor for peritoneal dissemination and was associated with shorter survival. Immunohistochemical staining of primary carcinomas showed ACP5 to be expressed mainly in the cytoplasm. CONCLUSION: ACP5 is predictive of peritoneal dissemination in patients with gastric cancer, and might play a crucial role in the establishment of peritoneal dissemination.
Berlth F, Mönig SP, Schlösser HA, et al. Validation of 2-mm tissue microarray technology in gastric cancer. Agreement of 2-mm TMAs and full sections for Glut-1 and Hif-1 alpha. Anticancer Res. 2014; 34(7):3313-20 [PubMed] Related Publications
BACKGROUND/AIM: Tissue Microarray (TMA) is a widely used method to perform high-throughput immunohistochemical analyses on different tissues by arraying small sample cores from paraffin-fixed tissues into a single paraffin block. TMA-technology has been validated on numerous cancer tissues and also for gastric cancer studies, although it has not been validated for this tumor tissue so far. The objective of this study was to assess, whether the 2-mm TMA-technology is able to provide representative samples of gastric cancer tissue. MATERIALS AND METHODS: TMA paraffin blocks were constructed by means of 220 formalin-fixed and paraffin-embedded gastric cancer samples with a sample diameter of 2 mm. The agreement of immunohistochemical stainings of Glut-1 and Hif-1 alpha in TMA sections and the original full sections was calculated using kappa statistics and direct adjustment. RESULTS: The congruence was substantial for Glut-1 (kappa 0.64) and Hif-1 alpha (kappa 0.70), but with an agreement of only 71% and 52% within the marker-positive cases of the full-section slides. CONCLUSION: Due to tumor heterogeneity primarily, the TMA technology with a 2-mm sample core shows relevant limitations in gastric cancer tissue. Although being helpful for tissue screening purposes, the 2-mm TMA technology cannot be recommended as a method equal to full-section investigations in gastric cancer.
Sparks D, Bhalla A, Dodge J, Saldinger P Isolated gastric amyloidoma in the setting of marginal zone MALT lymphoma: case report and review of the literature. Conn Med. 2014; 78(5):277-80 [PubMed] Related Publications
A 52-year-old female presented with hematochezia. A computed topography (CT) scan revealed diffuse proximal gastric thickening with enlarged perigastric lymph nodes. The esophagogastroduodenoscopy (EGD) revealed a diffusely thickened gastric wall with hemorrhagic, friable mucosa, and multiple areas of ulceration. The biopsies showed diffuse amyloid deposition along with transmural proliferation of small- to medium-sized lymphocytes and plasma cells. The gastric mucosa showed lymphoepithelial lesions and chronic inactive gastritis. Immunohistochemical staining of the neoplastic lymphocytes revealed expression of CD20, bcl-2, bcl-10, Ki-67 proliferative index of 5%, and lambda light chain restriction. There was no expression of CD5, CD43, CD10, CD3, cyclin D1, and bcl-6. Immunophenotyping by flow cytometry revealed an abnormal B lymphocyte population with expression of CD45, CD19, CD20, and FMC7. The histomorphological, immunohistochemical and flow cytometric features were consistent with primary gastric amyloidosis associated with extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma).
Nakagawa M, Kitazawa R, Kondo T, et al. Duodenal gastric heterotopia, sporadic or fundic gland polyp-associated, frequently carries β-catenin mutation. Virchows Arch. 2014; 465(3):253-6 [PubMed] Related Publications
Duodenal gastric heterotopia (DGH) is a benign asymptomatic condition assumed to be of congenital origin. Since DGH is often associated with fundic gland polyps (FGPs) that frequently carry a somatic β-catenin gene mutation, we examined whether DGH, either sporadic or FGP-associated, is attributable to alterations of the Wnt/β-catenin pathway. Genetic analysis revealed frequent somatic β-catenin gene mutations in DGH; some of which showed the same mutation pattern as coexisting FGPs. All missense mutations were confined to codons 32, 33, and 37. No such mutations were observed, however, in any of the specimens from focal gastric foveolar metaplasia (GFM). Therefore, DGH is not a mere congenital lesion due to aberrant migration of normal gastric mucosa or a simple reactive metaplasia after regenerative stimuli of the duodenal mucosa, but a distinct condition based upon molecular genetic changes in the Wnt/β-catenin pathway.
Jang SH, Park JW, Kim HR, et al. ADRM1 gene amplification is a candidate driver for metastatic gastric cancers. Clin Exp Metastasis. 2014; 31(6):727-33 [PubMed] Related Publications
We searched for candidate target genes in metastatic gastric cancer, using comparative genomic hybridization (CGH) and mRNA expression array analysis of endoscopic biopsy samples collected from 32 patients. Recurrent amplicons included 17q21.2 (36,569,293-37,307,055), 8q24.13-q24.21 (126,357,475-130,159,285), and 20q13.33 (60,211,249-61,382,787). In this paper, we focused on the 1.1-Mb genomic region containing 24 genes in chromosome 20q13.33 (from 60,211,249 to 61,382,787), the third most frequent amplicon that was amplified in three of 32 patients (9.4 %), with log2 tumor/reference ratios ranging from 0.6 to 1.5. Of three genes in the 20q13.33 amplicon, ADRM1 was chosen for functional analyses. ADRM1 knockdown suppressed the proliferation of two human gastric cancer cells, SNU-601 and SNU-216. Overexpression of Adrm1 promoted cell proliferation of conditionally-immortalized, mouse ImSt gastric epithelial cells, with increased S1 phase fraction and decreased expression of p21(Cip1). These results collectively indicate that ADRM1 promoted gastric epithelial cell proliferation by cell cycle progression. Therefore, ADRM1 is a candidate target gene in the chromosome 20q13.33 amplicon that may possibly be linked to development of gastric cancer.