• Journal of Gastric Cancer
• /
• v.7 no.2
• /
• pp.74-81
• /
• 2007

Purpose: Routine pancreatico-splenectomy with total gastrectomy should no longer be considered as the standard surgical procedure for gastric cancer because of the lack of proven surgical benefit for survival. The aim of this study is to evaluate the clinicopathologic factors and the survival of patients with locally advanced gastric cancer and they had undergone combined pancreatico-splenectomy with a curative intent. Material and Methods: We retrospectively reviewed a total of 118 patients who had undergone total gastrectomy with distal pancreatico-splenectomy from 1990 to 2001. The patients were divided into 2 groups: 90 patients who were free from cancer invasion (group I), and 28 patients with histologically proven cancer invasion into the pancreas (group II). The various clinicopathologic factors that were presumed to influence survival and the survival rates were analyzed. Results: The rate of pathological pancreatic invasion was 23.7%. The tumor stage, depth of invasion, pancreas invasion, lymph node metastasis, lymph node ratio, curability and the hepatic and peritoneal metastasis were statistically significance on univariate analysis. Among these factors, the tumor stage, lymph node ratio and curability were found to be independent prognostic factor on multivariate analysis. The 5-years survival rates were 36.2% for group I and 13.9% for group II. The morbidity rate was 22.1%, and this included pancreatic fistula (5.1%), intra-abdominal abscess (4.2%) and bleeding (4.2%). The overall mortality rate was 0.8%. Conclusion: Combined distal pancreatico-splenectomy with total gastrectomy with a curative intent was selectively indicated for those patients with visible tumor invasion to the pancreas, a difficult complete lymph node dissection around the distal pancreas and spleen, and no evidence of liver metastasis or peritoneal dissemination.

• Biomolecules & Therapeutics
• /
• v.21 no.5
• /
• pp.338-342
• /
• 2013

Sphingosylphosphorylcholine (SPC) is significantly increased in the malicious ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments in PANC-1 cells. The reorganization contributes to the viscoelasticity of metastatic cancer cells resulting in increased migration. Recently, we reported that transglutaminase-2 (Tgase-2) is involved in SPC-induced K8 phosphorylation and reorganization. However, effects of Tgase-2 inhibitors on SPC-induced K8 phosphorylation and reorganization were not clearly studied. We found that ethacrynic acid (ECA) concentration-dependently inhibited Tgase-2. Therefore, we examined the effects of ECA on SPC-induced K8 phosphorylation and reorganization. ECA concentration-dependently suppressed the SPC-induced phosphorylation and perinuclear reorganization of K8. ECA also suppressed the SPC-induced migration and invasion. SPC induced JNK activation through Tgase-2 expression and ECA suppressed the activation and expression of JNK in PANC-1 cells. These results suggested that ECA might be useful to control Tgase-2 dependent metastasis of cancer cells such as pancreatic cancer and lung cancers.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.21
• /
• pp.9523-9527
• /
• 2014

The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow-up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.36 no.1
• /
• pp.1-6
• /
• 2010

Purpose: Chemokines are structurally related, small polypeptide signaling molecules that bind to and activate a family of transmembrane G protein-coupled receptors, the chemokine receptors. Recently, interaction between the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12), has been found to play an important role in tumorigenicity, proliferation, metastasis and angiogenesis in many cancers such as lung cancer, breast cancer, melanoma, glioblastoma, pancreatic cancer and cholangiocarcinoma. Hence, the goal of this study is to identify the correlation of clinicopathological factors and the up-regulation of SDF-1 expression in oral squamous cell carcinoma. Material and methods: We studied the immunohistochemical staining of SDF-1, quantitative RT-PCR (qRT-PCR) of SDF-1 gene in 20 specimens of 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poor differentiated and invasive oral squamous cell carcinoma, the high level staining of SDF-1 was observed. And the correlation between immunohistochemical SDF-1 expression and tumor nodes metastases (TNM) classification of specimens was significant.($x^2$ test, P < 0.05) 2. In the SDF-1 gene qRT-PCR analysis, SDF-1 expression was more in tumor tissue than in carcinoma in situ tissue. Paired-samples analysis determined the difference of SDF-1 mRNA expression level between the cancer tissue and the carcinoma in situ tissue.(Student's t-test, P < 0.05) Conclusion: These findings suggest that up-regulation of the SDF-1 may play a role in progression and invasion of oral squamous cell carcinoma.

• Molecules and Cells
• /
• v.41 no.6
• /
• pp.591-602
• /
• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.473-481
• /
• 2020

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDA-MB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.

• Journal of Life Science
• /
• v.26 no.9
• /
• pp.1056-1062
• /
• 2016

Lung cancer is currently the most common malignant disease and the leading cause of mortality in the world and non-small cell lung cancer (NSCLC) accounts for 75-80% of lung cancer cases. miR-155 gene was found to be over expressed in several solid tumors, such as thyroid carcinoma, breast cancer, colon cancer, cervical cancer, pancreatic ductal adenocarcinoma (PDAC) and lung cancer. The aims of this study were to define the expression of miR-155 in lung cancer and its associated clinic-pathologic characteristics. Total RNA was purified from formalin-fixed, paraffin-embedded NSCLC tissues and benign lung tissues. Expression of miR-155 in human lung cancer tissues were evaluated as mean fold changes of miR-155 in cancer tissues compared to benign lung tissues by quantitative real-time reverse transcriptase polymerase chain reaction (real-time qRT-PCR) and associations of miR-155 expression with clinic-pathologic findings of cancer. Compared with the benign control group, miR-155 expression was significantly overexpressed in NSCLCs (p=<0.001). miR-155 was more overexpressed in squamous cell carcinoma than in adenocarcinoma. Poorly differentiated tumors showed significantly overexpression of miR-155 than well-differentiated tumors (p=<0.001). Overexpression of miR-155 was significantly associated with lymph node metastasis (p=<0.05). In survival analysis for all NSCLC patients, high miR-155 expression was significantly correlated with worse overall survival (p=<0.05). These results suggested that miR-155 might play an important role in lung cancer progression and metastasis.

• The Korean Journal of Pain
• /
• v.3 no.2
• /
• pp.108-118
• /
• 1990

Splanchnic nerve block (SNB) is performed to relieve intractable upper abdominal pain caused by carcinoma of the upper G-I tract. Not all patients achieve satisfactory pain relief; therefore, a second or third nerve block trial may need to be performed. In this study, an attempt was made to analyze the possible factors which might affect the result of repeated SNB in 42 the patients among 264 patients who received SNB at Severance Hospital during the period from January 1985 to December 1989. The results are as follows: 1) Among the 42 patients, including 30 males and 12 females, the fifties and forties were the major age groups. 2) Among the underlying diseases, stomach cancer was the most common (18 cases) and pancreatic cancer was next (14 cases). 3) The main locations of pain were the upper abdomen, epigastrium and entire abdomen in decreasing order. 4) Among the thirty-nine cases of first SNB combined with ascites, 13 cases received a repeat block, 81.0% of whom had had metastatic lesion. 5) There were 54.2% who had had single or combined treatment, operation, chemotherapy or radiotherapy before SNB. 6) Twently seven cases (64.3%) had received opioid medication for pain control. 7) In the 75% alcohol group, 11.7% of patients required a second block, and in the pure and 50% alcohol group, 9.6% of patients required a second block within two weeks of the first block. Three cases in both of these repeated block groups required a third block; representing 3.9%, of the 75% alcohol group and 1.6% of the pure and 50% alcohol group. 8) The volume of alcohol used was more than 16 ml bilaterally in both cases. 9) The points of the inserted needle were positioned in the upper and anterolateral part of the $L_1$ vertebra on both sides on the anteroposterior roentgenogram. The contrast media was spread upward along the anterior margin of the vertebral body and posteriorly in repeat block. The frequency of repeat block was higher in cases with ascites or metastasis. The instance of repeat block within 2 weeks of the first block was lower in the pure and 50% alcohol group than in the 75% alcohol group. Thus, alcohol concentration and patient status may be considered factors which influence the result of repeated SNB. We suggest early application of SNB in upper abdominal cancer patients.

• Journal of Food Hygiene and Safety
• /
• v.31 no.1
• /
• pp.59-66
• /
• 2016

It has been generally accepted that obesity and overweight are associated with metabolic diseases and cancer incidence. In fact, obesity increased risks of cancers i.e. breast, liver, pancreatic and prostate. Celastrol is a pentacyclic triterpenoid isolated from Thunder god vine, was used as a Chinese traditional medicine for treatment of inflammatory disorders such as arthritis, lupus erythematosus and Alzheimer's disease. Also, celastrol has various biological properties of chemo-preventive, neuro-protective, and anti-oxidant effects. Recent studies demonstrated that celastrol has anti-proliferation effects in different type of obesity-related cancers and suppresses tumor progression and metastasis. Anticancer effects of celastrol include regulation of $NF-{\kappa}B$, heat shock protein, JNK, VEGF, CXCR4, Akt/mTOR, MMP-9 and so on. For these reasons, celastrol has shown to be a promising anti-tumor agent. In this review, we will address the anticancer activities and multiple mechanisms of celastrol in obesity-related cancers.

• Journal of Hospice and Palliative Care
• /
• v.23 no.1
• /
• pp.5-10
• /
• 2020

Purpose: The aim of this study was to investigate celiac plexus neurolysis (CPN) for the treatment of cancerous upper abdominal pain in a tertiary university hospital in Korea. Methods: At the tertiary university hospital in Korea, electronic medical records of cancer patients who underwent CPN and died in the hospital from November 2009 to June 2018 were retrospectively analyzed. Results: The total number of subjects was 51. The 17 patients were from the Department of Gastroenterology (33.0%), followed by 11 patients from the Department of Hemato-oncology (21.6%), 11 patients from the Department of Anesthesia and Pain Medicine (21.6%), 9 patients from the Department of General Surgery (17.6%). The diagnosis was pancreatic cancer in 15 patients (29.4%), stomach cancer in 8 patients (15.7%), hepatobiliary cancer in 20 patients (39.2%), colon cancer in 1 patient (2.0%), esophageal cancer in 2 patient (3.9%) and intra-abdominal metastasis in 5 patients (9.8%). The mean survival time after the surgery was 66.4±55.0 days. The pain intensity before and 1 week after the procedure significantly decreased, but the amounts of opioids consumed before and 1 week after the procedure were not statistically significant. Side effects occurred after the procedure including temporary localized pain in 24 patients (47.0%), hypotension in 12 (23.5%), and diarrhea in 6 (11.8%). Conclusion: CPN is an effective and safe procedure for reducing upper abdominal pain caused by cancer, and it is necessary to perform CPN within the appropriate time by establishing a system of interdepartmental cooperation.