Livin is associated with the invasive and oncogenic phenotypes of human hepatocellular carcinoma cells.

AIM: Livin, a member of the inhibitors of apoptosis proteins, is expressed in variable cancers, and its expression is considered a poor prognostic marker. The aims of this study were to observe the effect of Livin on the behaviors of hepatocellular carcinoma (HCC) cells and to evaluate its expression in HCC tissues and its relation to prognosis. METHODS: The biological effects of Livin on tumor cell behavior were investigated using siRNA in HepG2 and Chang cells. Migration, invasion and proliferation assays were performed. Flow cytometric analyses and western blotting were used to evaluate the impact of Livin on apoptosis and the cell cycle. In addition, western blotting and immunohistochemistry were used to investigate Livin expression in HCC tissues. RESULTS: Livin knockdown suppressed tumor cell migration, invasion and proliferation in HCC cells, and increased the proportion of apoptotic cells as compared with scrambled siRNA-transfected HCC cells. Furthermore, Livin knockdown resulted in the activation of caspases and increased apoptosis. In addition, Livin knockdown modulated cell cycle regulatory protein levels such as decrease of cyclins and cyclin-dependent kinase (CDK) level, and increase of CDK inhibitor (CDKI) level in HCC cells. The Livin protein level was significantly elevated in HCC tissues as compared with normal hepatic tissues. However, Livin expression was not found to be associated with clinicopathological parameters, which included patient survival. CONCLUSION: These results suggest that Livin is associated with invasive and oncogenic phenotypes of human HCC cells.

Knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells.

BACKGROUND/AIMS: Altered Recepteur d'Origine nantais (RON) expression transduces signals inducting invasive growth phenotype that includes cell proliferation, migration, matrix invasion, and protection of apoptosis in human cancer cells. The aims of the current study were to evaluate whether RON affects tumor cell behavior and cellular signaling pathways including activator protein-1 (AP-1) and Akt/forkhead box O (FoxO) in human colorectal cancer cells. METHODS: To study the biological role of RON on tumor cell behavior and cellular signaling pathways in human colorectal cancer, we used small interfering RNA (siRNA) to knockdown RON gene expression in human colorectal cancer cell line, DKO-1. RESULTS: Knockdown of RON diminished migration, invasion, and proliferation of human colorectal cancer cells. Knockdown of RON decreased AP-1 transcriptional activity and expression of AP-1 target genes. Knockdown of RON activated cleaved caspase-3, -7, -9, and PARP, and down-regulated the expression of Mcl-1, survivin and XIAP, leading to induction of apoptosis. Knockdown of RON induced cell cycle arrest in the G2/M phase of cancer cells by an increase of p27 and a decrease of cyclin D3. Knockdown of RON inhibited the phosphorylation of Akt/FoxO signaling proteins such as Ser473 and Thr308 of Akt and FoxO1/3a. CONCLUSIONS: These results indicate that knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells.

RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer.

The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study were to evaluate whether RON affects tumor cell behaviors and oncogenic signaling pathways, and to document the relationship of its expression with various clinicopathological parameters in gastric cancer. The biological role of RON in tumor cell behaviors and oncogenic signaling pathways was investigated by using small interfering RNA in gastric cancer cell lines including AGS and MKN28. The expression of RON in gastric cancer tissues was investigated by using reverse transcription polymerase chain reaction and immunohistochemistry. Knockdown of RON suppressed tumor cell migration and invasion in AGS and MKN28, induced apoptosis through modulation of anti-apoptotic and pre-apoptotic genes and induced cell cycle arrest by decreasing cyclin D1, cyclin D3 and CDK4, and by inducing p21 and p27 expression. Signaling cascades, including Akt and mitogen-activated protein kinase (MAPK), were significantly blocked by knockdown of RON. Expression of RON was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer.

Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis.

BACKGROUND: Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE) on lipopolysaccharide (LPS)-induced NF-κB signaling in bone marrow derived-macrophages (BMM) and determined the therapeutic efficacy of this extract on colon inflammation. METHODS: The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS)-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores. RESULTS: LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1ß mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) in DSS-exposed mice was blocked by BTE. CONCLUSIONS: These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

Endoscopic ultrasonographic characteristics of gastric schwannoma distinguished from gastrointestinal stromal tumor.

BACKGROUND/AIMS: Gastric schwannoma (GS), a rare neurogenic mesenchymal tumor, is usually benign, slow-growing, and asymptomatic. However, GS is often misdiagnosed as gastrointestinal stromal tumors (GIST) on endoscopic and radiological examinations. The purpose of this study was to evaluate EUS characteristics of GS distinguished from GIST. METHODS: A total of 119 gastric subepithelial lesions, including 31 GSs and 88 GISTs, who were histologically identified and underwent EUS, were enrolled in this study. We evaluated the EUS characteristics, including location, size, gross morphology, mucosal lesion, layer of origin, border, echogenic pattern, marginal halo, and presence of an internal echoic lesion by retrospective review of the medical records. RESULTS: GS patients comprised nine males and 22 females, indicating female predominance. In the gross morphology according to Yamada's classification, type I was predominant in GS and type III was predominant in GIST. In location, GSs were predominantly located in the gastric body and GISTs were predominantly located in the cardia or fundus. The frequency of 4th layer origin and isoechogenicity as compared to the echogenicity of proper muscle layer was significantly more common in GS than GIST. Although not statistically significant, marginal halo was more frequent in GS than GIST. The presence of an internal echoic lesion was significantly more common in GIST than GS. CONCLUSIONS: The EUS characteristics, including tumor location, gross morphology, layer of origin, echogenicity in comparison with the normal muscle layer, and presence of an internal echoic lesion may be useful in distinguishing between GS and GIST.

Clinical impact of prophylactic antibiotic treatment for self-expandable metallic stent insertion in patients with malignant colorectal obstruction.

Purpose. The aim of this study was to determine the efficacy of prophylactic antibiotics (PA) for reducing the infectious complications and the potential risk factors responsible for the infectious complications after stent insertion for malignant colorectal obstruction. Methods. We performed a retrospective review of 224 patients who underwent self-expandable metallic stent (SEMS) insertion for malignant colorectal obstruction from May 2004 to December 2012. Results. There were 145 patients in the PA group and 79 in non-PA group. The CRP level in PA group was significantly higher than that in non-PA. Abdominal tenderness and mechanical ileus were significantly more frequent in PA group than those in non-PA. The frequency of post-SEMS insertion fever, systemic inflammatory response syndrome (SIRS), and bacteremia was not significantly different between PA and non-PA groups. In multivariate analysis, the CRP level was risk factor related to post-SEMS insertion SIRS. However, in propensity score matching analysis, there was no independent risk factor related to post-SEMS insertion fever, SIRS, and bacteremia. Conclusion. The use of PA in patients with malignant colorectal obstruction may be not effective to prevent the development of infectious complications after SEMS insertion.

Myeloid cell leukemia-1 promotes epithelial-mesenchymal transition of human gastric cancer cells.

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during cancer progression, and cancer stem cells have been shown to acquire the EMT phenotype. Myeloid cell leukemia-1 (Mcl-1) has been implicated in cancer progression and is overexpressed in a variety of human cancers. However, the interaction between Mcl-1 and EMT in human gastric cancer (GC) is unclear. We investigated the impact of Mcl-1 expression levels on EMT and the underlying signaling pathways in human GC cells. We used the human GC cell lines, AGS and SNU638, and small interfering RNAs (siRNAs) to evaluate the effects of Mcl-1 knockdown on cell adhesion, migration and invasion. Expression of Mcl-1 and other target genes was determined using reverse transcription-polymerase chain reaction assays and western blotting. The results revealed that expression levels of Mcl-1 mRNA and protein in the AGS and SNU638 cells were reduced following transfection with Mcl-1 siRNAs. Knockdown of Mcl-1 led to increased cellular adhesion to fibronectin and collagen. Expression levels of vimentin, MMP-2, MMP-9 and Snail protein were decreased following knockdown of Mcl-1. However, expression of E-cadherin was increased in the AGS cells following knockdown of Mcl-1. The expression of cancer stemness markers, such as CD44 and CD133, was not altered by knockdown of Mcl-1. Knockdown of Mcl-1 suppressed tumor cell migration and invasion in both human GC cell lines. Signaling cascades, including the ß-catenin, MEK1/2, ERK1/2 and p38 pathways, were significantly blocked by knockdown of Mcl-1. Our results indicate that Mcl-1 expression induces EMT via ß-catenin, MEK1/2 and MAPK signaling pathways, which subsequently stimulates the invasive and migratory capacity of human GC cells.

Myeloid cell leukemia-1 is associated with tumor progression by inhibiting apoptosis and enhancing angiogenesis in colorectal cancer.

Myeloid cell leukemia-1 (Mcl-1) is a highly expressed anti-apoptotic Bcl-2 protein in cancer. Therefore, inhibition of its expression induces apoptosis in cancer cells and enhances sensitivity to cancer treatment. The aims of this study were to evaluate whether Mcl-1 affects the oncogenic behaviors of colorectal cancer cells, and to document the relationship of its expression with various clinicopathological parameters in colorectal cancer. Mcl-1 knockdown induced apoptosis by activating cleaved caspase-3 and -9, and increasing the expression of the pro-apoptotic protein, PUMA. Mcl-1 knockdown induced cell cycle arrest by decreasing cyclin D1, CDK4 and 6, and by increasing p27 expression. Mcl-1 knockdown decreased both endothelial cell invasion and tube formation, and decreased the expression of VEGF. The phosphorylation level of STAT3 was decreased by Mcl-1 knockdown. The mean apoptotic index value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. The mean microvessel density value of Mcl-1 positive tumors was significantly higher than that of negative tumors. Mcl-1 expression was significantly increased in colorectal cancer, also associated with tumor stage, lymph node metastasis, and poor survival. These results indicate Mcl-1 is associated with tumor progression through its inhibition of apoptosis and enhancement of angiogenesis in colorectal cancer.

Association between interleukin-18 gene polymorphism and Helicobacter pylori infection in the Korean population.

Interleukin-18 (IL-18) is a pleiotropic, pro-inflammatory cytokine that is capable of promoting the Th1 response. A predominant Th1 response induces chronic and persistent inflammatory changes in the gastric mucosa in response to Helicobacter pylori (H. pylori) infection. The aim of this study was to investigate the potential association between IL-18 gene polymorphisms and susceptibility to H. pylori infection in the Korean population. A total of 678 subjects who underwent a routine health check-up were enrolled. The IL-18 gene polymorphisms at positions -656, -607, -137, +113, and +127 were genotyped. H. pylori positivity was demonstrated in 456 subjects (67.3%). The allele frequencies of IL-18 gene polymorphisms at position -137 (rs187238) were different based on the status of H. pylori infection (G vs. C, adjusted OR 0.64 CI: 0.47-0.87, P = 0.005). The results indicate that the genetic variants in the IL-18 gene may be associated with susceptibility to H. pylori infection in the Korean population, suggesting that IL-18 plays a role in the pathogenesis of H. pylori-associated diseases. However, this finding requires further replication and validation.

Myeloid cell leukemia-1 regulates the cell growth and predicts prognosis in gastric cancer.

The expression of myeloid cell leukemia-1 (Mcl­1), a member of the anti-apoptotic Bcl-2 protein family, has been associated with tumor progression and adverse patient outcome. The aims of current study were to evaluate whether Mcl-1 affects the survival or death of gastric cancer cells, and to investigate the prognostic value of its expression in gastric cancer. PcDNA3.1-Mcl-1 expression and Mcl-1 siRNA vectors were used to overexpress and silence Mcl-1 expression in gastric cancer cell lines including SNU638 and TMK1, respectively. Immunohistochemistry was used to determine the expression of Mcl-1 in gastric cancer tissues. Apoptosis was determined by the TUNEL assay, and cell proliferation was determined by immunostaining with a Ki-67 antibody. Mcl-1 knockdown induced apoptosis through the upregulation of caspase-3, and -7, and PARP activity, and the release of Smac/DIABLO and Omi/HtrA2 into the cytoplasm. Additionally, cell cycle arrest occurred due to decrease of cyclin D1, cell division cycle gene 2 (cdc2), and cyclin-dependent kinase 4 and 6. In contrast, overexpression of Mcl-1 inhibited apoptosis and cell cycle arrest. Mcl-1 knockdown did not suppress tumor cell proliferation in gastric cancer cells, whereas overexpression of Mcl-1 enhanced tumor cell proliferation. The JAK2 and STAT3 signaling cascades were significantly blocked by Mcl-1 knockdown. The mean Ki-67 labeling index (KI) value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. However, there was no significant difference between Mcl-1 expression and the apoptotic index (AI). Mcl-1 expression was significantly increased in gastric cancer tissues compared to normal gastric mucosa tissues, and was associated with age, tumor size, stage, depth of invasion, lymph node metastasis and poor survival. Our study showed that Mcl-1 regulates the cell growth and might be a potential prognostic marker for gastric cancer.

Coexistence of solitary rectal ulcer syndrome and ulcerative colitis: a case report and literature review.

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease that is misdiagnosed as malignancy or inflammatory bowel disease because of similarities in clinical and endoscopic manifestations. Furthermore, SRUS with ulcerative colitis (UC) is extremely rare. To date, two cases have been reported in the medical literature. We report an additional case of SRUS with UC that was misdiagnosed as rectal cancer. A 61-year-old man was admitted to our hospital with rectal bleeding. Colonoscopy showed a well-demarcated, shallow, ulcerative lesion with polypoidal growth involving the entire circumference of the rectal lumen. Findings from imaging studies, including abdominal computed tomography (CT) and positron emission tomography (PET)/CT resembled those of rectal cancer. Surgical resection was performed because clinical symptoms persisted despite medical treatment and because occult rectal cancer could not be ruled out. Histopathological examination of the resected specimen revealed fibromuscular obliteration of the lamina propria and crypt abscesses, characteristics compatible with SRUS and UC.

Acute obstructive cholangitis complicated by tumor migration after transarterial chemoembolization: a case report and literature review.

Intraductal tumor invasion of hepatocellular carcinoma (HCC) is considered rare. Transarterial chemoembolization (TACE) is effective for tumor thrombus of HCC in the bile duct. However, a few cases of obstructive jaundice caused by migration of a tumor fragment after TACE have recently been reported. The aim of this study was to identify factors that affect tumor migration after TACE. At this writing, a review of the medical literature disclosed seven reported cases of biliary obstruction caused by migration of a necrotic tumor cast after TACE. We, herein, report on an additional case of acute obstructive cholangitis complicated by migration of a necrotic tumor cast after TACE for intrabile duct invasion of HCC, in a 71-year-old man. The tumor cast in the common bile duct was removed successfully using a basket during ERCP and was pathologically confirmed to be a completely necrotic fragment of HCC. The patient's symptoms showed dramatic improvement. In summary, physicians should be aware of acute obstructive cholangitis complicated by tumor migration in a patient undergoing TACE. We suggest that an intrabile duct invasion would be a major predisposing factor of tumor migration after TACE and drainage procedures such as ERCP or percutaneous transbiliary drainage could be effective treatment modalities in these patients.

The need for second-look endoscopy to prevent delayed bleeding after endoscopic submucosal dissection for gastric neoplasms: a prospective randomized trial.

BACKGROUND/AIMS: Many authors recommend performing a second-look endoscopy (SLE) to reduce the frequency of delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasms, but these recommendations have been made despite a lack of reliable evidence supporting the effectiveness of SLE. METHODS: From January 2012 to May 2013, we investigated 441 gastric neoplasms treated by ESD to assess the risk factors for delayed bleeding. Delayed bleeding occurred in four of these lesions within 1 postoperation day. Therefore, we enrolled the patients with the remaining 437 lesions to determine the utility of SLE performed on the morning of postoperative day 2. All lesions were randomly assigned to SLE (220 lesions) groups or non-SLE (217 lesions) groups. RESULTS: Delayed bleeding occurred in 18 lesions (4.1%). A large tumor size (>20 mm) was the only independent risk factor for delayed bleeding (p=0.007). The chance of delayed bleeding was not significantly different between the patients receiving a SLE (eight cases) and those patients not receiving a SLE (six cases, p=0.787). Furthermore, SLE for lesions with a large tumor size did not significantly decrease delayed bleeding (p=0.670). CONCLUSIONS: SLE had little or no influence on the prevention of delayed bleeding, irrespective of the risk factors.

Expression of early growth response-1 in colorectal cancer and its relation to tumor cell proliferation and apoptosis.

Early growth response-1 (Egr-1) is implicated in the regulation of cell growth, proliferation, differentiation and apoptosis. Egr-1 is considered tobe either a tumor-suppressor or tumor-promoter, depending on the cell type and environment. The aim of the present study was to evaluate the expression of Egr-1 in colorectal cancer and its correlation with tumor cell proliferation, apoptosis and clinicopathological features. The expression of Egr-1 in colorectal cancer tissues was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and cellular proliferative activity was evaluated by immunohistochemical staining with the Ki-67 antibody. Egr-1 expression was significantly elevated in colorectal cancer tissues, when compared to that in the paired normal mucosa at the mRNA and protein levels. In addition, Egr-1 expression was significantly increased in the metastatic lymph node tissues, when compared to that in the non­metastatic lymph node tissues at the protein level. The mean Ki-67 labeling index (KI) and apoptotic index (AI) values for 158 tumors were 53.6±15.4 and 9.0±1.0, respectively. Higher KI values were significantly associated with distant metastasis. Lower AI values were significantly associated with lymph node metastasis. However, KI or AI values were not associated with patient survival. The mean KI value of Egr-1-positive tumors was significantly higher than that of Egr-1-negative tumors. However, there was no significant difference between Egr-1 expression and AI value. Positive expression of Egr-1 was significantly associated with age, lymphovascular invasion, lymph node and distant metastasis, tumor stage and poor survival. These results indicate that Egr-1 may be associated with colorectal cancer progression via tumor cell proliferation.

Parathyroid cyst presenting as acute pancreatitis: report of a case.

We report the first case of hypercalcemia-induced acute pancreatitis caused by a functioning parathyroid cyst in a 67-year-old man. Laboratory investigation revealed increased serum amylase and lipase, increased serum ionized calcium and parathyroid hormone (PTH) levels, and decreased serum phosphate, indicating pancreatitis and primary hyperparathyroidism (PHPT). Abdominal computed tomography (CT) revealed mild swelling of the pancreatic head with peri-pancreatic fat infiltration and fluid collection around the pancreatic tail. Ultrasonography and CT of the neck showed a cystic lesion at the inferior portion of the left thyroid gland, suggesting a parathyroid cyst. There was no evidence of parathyroid adenoma by 99mTc sestamibi scintigraphy. PHPT caused by a functioning parathyroid cyst was suspected. The patient underwent surgical resection of the functioning parathyroid cyst owing to his prolonged hypercalcemia. At 3 weeks after the operation, his serum levels of PTH, total calcium, ionized calcium, inorganic phosphate, amylase, and lipase were normalized. At the follow-up examinations, he has remained asymptomatic.

Synchronous quadruple primary tumors of thyroid, breast, pancreas, and stomach: a case report.

We herein present the first case to be reported of synchronous quadruple primary cancer of the thyroid, breast, pancreas and stomach in a 70-year-old female. Fluorine-18-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) revealed increased FDG activity in the thyroid, left breast, pancreatic body and antrum of the stomach. To make a definitive diagnosis of synchronous quadruple primary tumors, ultrasound-guided fine-needle aspiration (FNA) cytology and biopsy of the thyroid, breast, pancreas and stomach were performed. FNA cytology and biopsy findings showed papillary carcinoma of the thyroid, invasive ductal adenocarcinoma of the breast, adenocarcinoma of the pancreas and gastrointestinal stromal tumor. To the best of our knowledge, this combination of synchronous multiple primary tumors has not been reported.

Cerebral and splenic infarctions after injection of N-butyl-2-cyanoacrylate in esophageal variceal bleeding.

Variceal bleeding is the most serious complication of portal hypertension, and it accounts for approximately one fifth to one third of all deaths in liver cirrhosis patients. Currently, endoscopic treatment remains the predominant method for the prevention and treatment of variceal bleeding. Endoscopic treatments include band ligation and injection sclerotherapy. Injection sclerotherapy with N-butyl-2-cyanoacrylate has been successfully used to treat variceal bleeding. Although injection sclerotherapy with N-butyl-2-cyanoacrylate provides effective treatment for variceal bleeding, injection of N-butyl-2-cyanoacrylate is associated with a variety of complications, including systemic embolization. Herein, we report a case of cerebral and splenic infarctions after the injection of N-butyl-2-cyanoacrylate to treat esophageal variceal bleeding.

Expression of Livin in colorectal cancer and its relationship to tumor cell behavior and prognosis.

BACKGROUNDS: Expression of Livin, a member of the inhibitors of apoptosis protein family, is associated with tumor development and progression. The aims of this study were to evaluate whether Livin affects oncogenic biological behavior of colorectal cancer cells, and to document the relationship between its expression and various clinicopathological parameters in colorectal cancer. METHODS: We investigated the impact of Livin on tumor cell behavior by using the small interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell lines. The expression of Livin was investigated by RT-PCR and immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were visualized by TUNEL assay, and proliferative cells were visualized by Ki-67 antibody staining. RESULTS: Knockdown of Livin suppressed tumor cell migration and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by inducing p27 expression. The MAPK signaling cascades were significantly blocked by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell migration and invasion, and inhibited the apoptosis and cell cycle arrest. The mean apoptotic index (AI) value of Livin positive tumors was significantly lower than AI of Livin negative tumors. However, there was no significant difference between Livin expression and Ki-67 labeling index (KI). Livin expression was significantly increased in colorectal cancer and metastatic lymph node tissues compared to normal colorectal mucosa and non-metastatic lymph node tissues and was associated with tumor stage, lymphovascular invasion, lymph node metastasis and poor survival. CONCLUSIONS: These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.

Expression and prognostic significance of Livin in gastric cancer.

Livin is one of the most important members of the inhibitor of apoptosis protein family. It is overexpressed in several types of tumors and may have prognostic significance. The present study investigated the biological role of Livin in the oncogenic behavior of gastric cancer cells, the expression of Livin in gastric cancer tissue and the relationship of its expression with various clinicopathological parameters and patient survival. Small interfering RNA blocked Livin gene expression in AGS and SNU638 human gastric cancer cell lines. The expression of Livin was investigated in gastric cancer tissues by RT-PCR, western blotting and immunohistochemistry. The associations with various clinicopathological parameters and survival were analyzed. Livin knockdown inhibited tumor cell migration, invasion and proliferation in AGS and SNU638 cells. Livin knockdown induced apoptosis by activating caspase-3, caspase-7 and PARP. Livin knockdown induced cell cycle arrest by a decrease in cyclin D1, cyclin-dependent kinase 4 and 6 and an increase in expression of p21 and p27. The ERK1/2 and JNK signaling pathways were inhibited by Livin knockdown. Livin expression was upregulated in gastric cancer tissues at the mRNA and protein levels. However, no significant correlation was found between Livin expression and various clinicopathological parameters including survival. In conclusion, Livin expression may be important in the alteration of invasive and oncogenic phenotypes of gastric cancer cells. The prognostic relevance of Livin remains unclear.

Expression of early growth response-1 in human gastric cancer and its relationship with tumor cell behaviors and prognosis.

The early growth response-1 (Egr-1) is crucial in many cell regulatory processes related to the progression of human cancers. Its overexpression has been demonstrated in variable human cancers and may have prognostic significance. The aims of this current study were to evaluate whether Egr-1 affects invasive and oncogenic phenotypes of human gastric cancer cells, and to examine the relationships between its expression and various clinicopathological parameters, including survival in human gastric cancer patients. We investigated the biologic role of Egr-1 in tumor cell behavior by using a small interfering RNA in human gastric cancer cell lines, AGS and TMK1. The expression of Egr-1 by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry was investigated in human gastric cancer tissues. The knockdown of Egr-1 suppressed tumor cell migration and invasion in AGS and TMK1 cells. Egr-1 expression was significantly increased in human gastric cancer and metastatic lymph node tissues compared to the normal gastric mucosa and non-metastatic lymph node tissues. Positive expression of Egr-1 was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that Egr-1 is associated with human gastric cancer progression through the alteration of tumor cell behavior, such as migration and invasion. Egr-1 expression may help in predicting the clinical outcomes of human gastric cancer patients.