• Nuclear Medicine and Molecular Imaging
• /
• v.42 no.sup1
• /
• pp.46-51
• /
• 2008

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract, and can be distinguished from the smooth muscle or neural tumors in approximately 95% of patients by expression of the KIT receptor tyrosine kinase (CD117). GISTs are known to have high malignant potential and none can be labeled definitely as benign. However, GISTs are unresponsive to standard sarcoma chemotherapy, and only complete surgical resection provides chance for cure. Although the imaging modality of choice is enhanced CT scan in patients with GIST, FDG PET can reflect the malignant potential of GIST. Clinical management of patients with GISTs has dramatically changed with the introduction of novel therapeutics, such as imatinib mesylate (Glivec). This has created a need to re-evaluate the existing criteria used to assess treatment response. FDG PET as functional imaging modality proved to be significantly more accurate than CT alone when assessing GIST response to imatinib. And, FDG PET and PET ICT have been found to be highly sensitive in detecting early response, and to be useful in predicting long-term response to imatinib in patients with recurrent or metastatic GISTs.

• Journal of Gastric Cancer
• /
• v.16 no.1
• /
• pp.1-7
• /
• 2016

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra-or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

• The Korean journal of helicobacter and upper gastrointestinal research
• /
• v.18 no.3
• /
• pp.162-167
• /
• 2018

Cancer specimens obtained via surgical resection or biopsy are generally used to understand tumor-associated alterations; however, those approaches cannot always be performed because of their invasive nature, and they may fail to reflect current tumor dynamics and drug sensitivity, which may change during the therapeutic process. Therefore, many research groups have focused on developing a non-invasive biomarker with the ability to monitor tumor dynamics. Circulating tumor cells (CTCs) are metastatic cells released from the primary tumor into the bloodstream. Hematogenous spreading of CTCs is a crucial step in the metastatic cascade, which leads to the formation of overt metastases. CTCs have attracted considerable attention because of their easy accessibility and their superiority over conventional tumor markers. Detecting CTCs is considered a valuable modality to determine prognosis and monitor response to systemic therapies in patients with gastric cancer. Moreover, molecular analyses of CTCs may provide important biological information for individual patients with cancer, which may lead to the development of personalized cancer treatment. In this article, we review potential roles and clinical applications of CTCs in patients with gastric cancer.

• Journal of Korean Medicine Rehabilitation
• /
• v.19 no.1
• /
• pp.91-102
• /
• 2009

Objectives : The present study was carried out investigate the anti-cancer effect of Salvia miltiorrhiza, Carydalis turtschaminovii and Reynoutria elliptica herbal acupuncture on solid tumor of rats induced by injection of RK3E-ras cells. Methods : RK3E-ras cells were injected on the right lumbar region of rats. After 1 weeks, the experimental rats were divided into four groups : Control group, Salvia miltiorrhiza herbal acupuncture group(SM), Carydalis turtschaminovii herbal acupuncture group(CT), Reynoutria elliptica herbal acupuncture group(RE). And we investigated the weight and size of tumor tissue, gross anatomy, histological and PCNA immunohistochemical study, hepatic and renal metastasis for tumor of each group. Results : 1. In the weight of tumor tissue assessment, SM and CT's weight of tumor tissue was decreased. 2. In the size of tumor tissue assessment, SM was smaller than any other group. 3. In the histological observation, SM's formation of tunica fibrosa that surround the tumor cell was obvious and vasculature that developes circumference of tumor cell was not observed, and density of tumor cell was very low. 4. In the PCNA immunohistochemical study, Control group, SM, RE showed strong immune response in the central site of tumor tissue. 5. In observation of liver and kidney tissue, we were not able to observe tumor cell in the SM. Conclusions : Consequently, SM and CT showed a inhibition of growth and metastasis.

• YAKHAK HOEJI
• /
• v.47 no.3
• /
• pp.159-166
• /
• 2003

In order to study the clinical usefulness of crude polysaccharides fractionated from Eleutherococcus senticosus, EN-3, in eliminating tumors, we have investigated the effect of combination therapy on the murine tumor metastasis and growth models. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous (i.v.) administration of EN-3 (0.5, 5, and 50 $\mu\textrm{g}$/mouse) inhibited tumor metastasis compared with tumor control group in 33.6, 66.8, and 81.8％ respectively. The administration of EN-3 (50 $\mu\textrm{g}$/mouse) also exhibited a 66.1％ therapeutic effect on lung tumor metastasis. Although EN-3 induced no toxic effect on both tumor cell and normal splenocyte in the concentration below 100 $\mu\textrm{g}$/mι in in vitro, it induced significant proliferating activity on normal splenocyte in the concentration-dependent manner. In an analysis of NK-cell activity, i.v. administration of EN-3 (4∼100 $\mu\textrm{g}$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin (10 $\mu\textrm{g}$) and EN-3 (5 $\mu\textrm{g}$) induced synergistic effect on the inhibition of tumor metastasis in experimental tumor metastasis model produced by colon26-M3.1 cells. In addition, the combination treatments also exhibited prolongation of lifespan in S∼180 tumor bearing mouse for over the 60 days. Even though cisplatin (2.5 $\mu\textrm{g}$/mι) exhibited cytotoxicity to tumor cells and inhibited tumor growth over 95％ in in vitro, combination treatment with EN-3 (20 $\mu\textrm{g}$/mι) was induced splenocyte proliferation and produced cytokines, such as TNF-$\alpha$, IL-1 and IL-12, from the macrophages. These results suggested that EN-3 stimulate immune system non-specifically and apply to the biological response modifiers (BRM) in chemo-immunotherapy for tumor prevention.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.5
• /
• pp.2003-2007
• /
• 2015

Background: Elevated serum alpha-fetoprotein (AFP) levels in adults are considered abnormal. This parameter is used mostly in the diagnosis and follow-up of hepatocellular carcinomas and yolk sac tumors. Among the other rare tumors accompanied with elevated serum AFP levels, gastric cancer is the most common. In this study, we evaluated the follow-up and comparison of the treatment and marker response of patients with metastatic gastric cancer who had elevated serum AFP levels. Materials and Methods: We performed a retrospective study, including all consecutive patients with advanced gastric cancer, who received systemic chemotherapy with elevated AFP level. Results: Seventeen metastatic gastric cancer patients with elevated AFP levels at the time of diagnosis were evaluated. Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor localization was the gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum in 2 (11.8%). Hepatic metastasis was observed in 13 (76.4%) at the time of diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA) response of the patients with their radiologic responses was evaluated, it was found that the radiologic response was compatible with AFP response in 16 (94.1%) patients and with CEA response in 12 (70.6%); however, in 5 (29.4%) patients no accordance was observed between radiological and CEA responses. Conclusions: Follow-up of AFP levels in metastatic gastric cancer patients with elevated AFP levels may allow prediction of early treatment response and could be more useful than the CEA marker for follow-up in response evaluation.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1111-1116
• /
• 2015

Background: To investigate the relationship between pathologic tumor response to concurrent chemoradiotherapy and variation of serum VEGF in patients with esophageal cancer. Materials and Methods: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. Results: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. Conclusions: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

• BMB Reports
• /
• v.55 no.4
• /
• pp.198-203
• /
• 2022

As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels.

• IMMUNE NETWORK
• /
• v.3 no.2
• /
• pp.96-102
• /
• 2003

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. Methods: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific $CD8^+$ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma ($IFN{\gamma}$), and cloned by limiting dilution. Results: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a $CD4^+/CD8^+$ double positive T cell clone (17/A2) appeared to recognize $IFN{\gamma}$-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after $IFN{\gamma}$ treatment. Conclusion: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by $IFN{\gamma}$.

• Nuclear Medicine and Molecular Imaging
• /
• v.42 no.sup1
• /
• pp.39-45
• /
• 2008

PET or PET/CT detects only less than 50% of early gastric cancer and 62-98% of advanced gastric cancer. Therefore, mass screening programs are recommended for all adults over the age of 40 for early detection and early treatment of gastric cancer through endoscopy or various radiological tests. The most important step after diagnosis of gastric cancer is accurate staging, which mainly evaluates tumor resectability to avoid unnecessary surgery. Important factors that affect tumor resectability are whether the tumor can be separated from adjacent organs or important blood vessels, the extent of lymph node metastasis, presence of peritoneal metastasis, or distant organ metastasis. To evaluate the extent of local tumor invasion, anatomical imaging that has superior spatial resolution is essential. There are a few studies on prognostic significance of FDG uptake with inconsistent results between them. In spite of lower sensitivity for lymph node staging, the specificity of CT and PET are very high, and the specificity for PET tends to be higher than that for CT. Limited data published so far show that PET seems less useful in the detection of lung and bone metastasis. In the evaluation of pleural or peritoneal metastasis, PET seems very specific but insensitive as well. When FOG uptake of primary tumor is low, distant metastasis also tends to show low FDG uptake reducing its detection on PET. There are only a few data available in the evaluation of recurrence detection and treatment response using FDG PET or PET/CT.