• IMMUNE NETWORK
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• 제21권4호
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• pp.31.1-31.16
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• 2021

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2^negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2^negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45⁺ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2^negative AGC.

• Clinical Endoscopy
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• 제56권1호
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• pp.83-91
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• 2023

Background/Aims: Double-balloon enteroscopy (DBE) allows for the diagnoses and treatment of small bowel tumors (SBTs). This study aimed to evaluate the utility of DBE for the diagnosis and treatment of SBTs. Methods: Patients diagnosed with SBTs who underwent DBE were included in this study. According to their endoscopic appearances, they were categorized as polyps or masses, and according to their histological characteristics, they were categorized as benign or malignant SBTs. Results: A total of 704 patients were retrospectively analyzed, and 90 (12.8%) were diagnosed with SBTs. According to their endoscopic appearance, 48 (53.3%) had polyps and 42 (46.7%) had masses. Additionally, 53 (58.9%) and 37 (41.1%) patients had malignant and benign SBTs, respectively, depending on their histological characteristics. Patients diagnosed with polyps were younger than those diagnosed with masses (p<0.001). Patients diagnosed with benign SBTs were younger than those diagnosed with malignant SBT (p<0.001). Overall, histological diagnosis was determined using DBE in 73 (81.1%) patients. Conclusions: DBE is a useful method for diagnosing SBTs. Additionally, the histological type of the lesion can be determined using DBE.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1677-1680
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• 2013

Background: Areas of Iran have among the highest incidences of esophageal cancer in the world. Definitive chemo-radiotherapy (DCRT) is used for locally advanced esophageal cancer and for inoperable tumors asan alternative to surgical treatment. Materials and Methods: This retrospective study was conducted in North-West Iran 2006-2011, including 267 consecutive patients with non-metastatic esophageal cancer. Eligible inoperable patients were treated with DCRT or definitive radiotherapy (DRT) alone. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. Results: The median survival was 12.7 months with 1, 3 and 5 year survival rates of 55%, 18% and 11%, respectively. On univariate analysis, relations with age at diagnosis (p=0.015), N-stage (p=0.04), total dose of RT (p=0.001), fraction (p<0.001), Gap status (p=0.025), chemotherapeutic regimens (P=0.027), and 5-Fu $Mg/m^2$ (P=0.004) were apparent. Comparing DCRT to DRT, there was a significant difference in survival. Multivariate analysis was performed for comparison between DCRT and DRT showed significant association with age group ${\geq}65$ to <65 (P=0.02; OR: 1.46), the total RT dose (Gy) ${\geq}50$ to <50 (P=0.01; OR: 0.65) and the fraction group ${\geq}25$ to <25 (P=<0.001; OR: 0.54). Conclusions: The survival rates of esophageal cancer treated with DCRT in North West of Iran is poor; therefore, early detection and improved treatment methods, with clinical trials are a high priority.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4751-4758
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• 2013

Background: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). Materials and Methods: Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. Results: Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (${\geq}30%$) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ${\geq}10/50HPF$ mitotic activity/HPF was the only independent factor for risk of death in GIST patients. Conclusions: Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.

• Journal of Chest Surgery
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• 제36권2호
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• pp.109-112
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• 2003

폐 형성에 활성적인 또는 억제적인 기능을 갖고 있다고 알려져 있는 FGF-7 성장인자, BMP수용체 II, 그리고 TGF-$\beta$ 수용체 II 유 전자의 비정상 발현이 폐기포 생성에 관여하는지를 각각의 단일성 클론 항체를 사용하여 수술로 절제된 자연기흉 환자의 폐기포 조직들을 면역조직염색 방법으로 염색하여 관찰하였다. 대상 및 방법: 재발성 또는 지속성 기흉으로 흉강경 또는 개흉술로 폐기포 절제술을 실시한 환자들을 대상으로 하였다. 총 31명의 환자로 15세에서 39세까지 연령분포를 보였으며 남자 30명, 여자 1명이었다. 폐기포 절제는 비디오흉강경이나 소절개개흉술을 통하여 폐기포벽의 손상을 가하지 않게 주의하면서 비디오흉강경용 스태플러(Endo GIA stapler)를 이용하여 절제하였으며 가능한 원형을 유지하여 신선한 상태로 포르마린에 고정하여 면역조직화학적 연구를 위한 표본을 만들었다. 폐기포 조직 슬라이드를 단일클론성 항 TGF-$\beta$ 수용체 II, BMP수용체 II 그리고 FGF-7인자 항체를 이용하여 면역조직학적 염색방법으로 관찰하였다. 결론: 전체 환자 31명중 TGF-$\beta$ 수용체 II항체에 양성 반응을 나타낸 환자수는 모두 24명이었다. 이들 중에는 18명이 강한 양성 반응을 보였고, 6명이 약한 양성 반응을 보였다. 면역조직화학적 염색 결과를 고배율 현미경으로 살펴보면, TGF-$\beta$ 수용체 II의 염색이 기흉과 정상 폐조직 경계 부위에서 특히 강하게 염색됨이 관찰되었다. 이에 반하여, BMP수용체 II 그리고 FGF-7인자의 항체를 이용한 면역조직학적 염색 결과는 모든 환자의 조직들에서 음성으로 관찰되었다. 절론: 폐 조직이 형성될 때, 억제유전자의 역할을 담당하고 있다고 알려진 TGF-$\beta$ 수용체 II의 발현이 증가되면서 폐기포가 생성될 수 있다는 가능성을 제시하였다. 이번 결론은 면역조직학적 염색 실험 결과만으로 밝혀진 사실임으로 좀 더 체계적인 분자생물학적 인 연구가 요구된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7149-7153
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• 2015

Background: Inflammation plays a major role in the development and progression of gastric and other gastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy. Materials and Methods: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients with gastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. Results: In only 5 (8.8%) of the patients' sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximum concentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in one of the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen between age and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in the same population. Conclusions: It is possible that the inflammopathology of CRC and GC are rather different, at least in Fars, a southern province of Iran.

• Journal of Chest Surgery
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• 제39권9호
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• pp.729-732
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• 2006

외상에 의하여 심장눌림증을 유발한 종격동 양성낭기형종 종격동 기형종은 전체 종격동 종양의 $8\sim13%$ 빈도로 발생하며, 대부분 우연히 발견되지만 드물게 심낭 천공이 발생하여 심장눌림증을 유발하거나, 흉막삼출액을 고이게 한다. 본 증례에서는 전흉벽 타박상을 받은 여자 환자에게서 심장눌림증이 발생하였고, 응급 방사선검사에서 종격전부 종양이 확인되었으며 심장막천자술을 받은 후 활력징후가 회복되어 추후 수술적 절제술로 종양을 적출하였다. 조직검사에서 피지선, 성숙 지방종, 위장관점막, 호흡기도 점막 및 췌장의 조직 등으로 구성된 낭포성 구조물로 관찰되어 양성 낭기형종으로 판정되었다.

• Journal of Preventive Medicine and Public Health
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• 제47권5호
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• pp.281-287
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• 2014

Objectives: In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. Methods: We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. Results: Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. Conclusions: The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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• pp.19-24
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• 2006

Mothers against decapentaplegic homolog 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study was to characterize more precisely its role in the development and progression of human gastric carcinoma. In this study, using tissue microarray analysis of 283 gastric cancers and related lesions, we found loss of SMAD4 protein expression in the cytoplasm (36/114, 32%) and in the nucleus (46/114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. To identify the genetic and/or epigenetic mechanisms of altered SMAD4 expression in gastric carcinoma, loss of heterozygosity (LOH), promoter hypermethylation, and exon mutations were examined. We found that LOH (20/70, 29%) and promoter hypermethylation (4/73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels wore also affected in certain gastric carcinoma cell lines following incubation with Mc132, a proteasome inhibitor. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.

• Nuclear Medicine and Molecular Imaging
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• 제41권4호
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• pp.335-336
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• 2007

Meniscus-like presentation of ulcerating gastric carcinoma on upper gastrointestinal series radiograph was first described in 1921 by Carman and has since been known as a useful differential diagnostic sign in radiology. In 1982 using then newly introduced computed tomography (CT) Widder and Mueller revisited the meniscus sign. Their study was primarily focused on a dynamic assessment of the demonstrability of the meniscus sign that largely depends on the judgment and technical skill of examiner, especially graded compression and patient positioning. One year earlier Balfe et al. assessed the diagnostic reliability of gastric wall thickening as observed on CT scan in adenocarcinoma, lymphoma and leiomyosarcoma and concluded that it is not a reliable finding. In contrast, however, Lee et al. recently emphasized that the wall thickness measurement on CT of exophytic carcinoma, myoma and ulcers was a useful diagnostic means. Thus, it appears that gastric wall thickening or mucosal heave-up is by itself not as reliable as the meniscus sign. The electronic search of world literature failed to disclose earlier report of this sign demonstrated by $^{18}F-FDG$ positron emission tomography and computed tomography (PET/CT). The present communication documents $^{18}F-FDG$ PET/CT finding of the meniscus sign as encountered in a case of ulcerating gastric carcinoma, the histological diagnosis of which was moderately differentiated tubular adenocarcinoma. Unlike most gastric tumors without ulceration that tend to unimpressively accumulate $^{18}F-FDG$ the present case of Borrmann type III gastric carcinoma demonstrated markedly increased $^{18}F-FDG$ uptake.