Is the construct stability of the acetabular cup affected by the acetabular screw configuration in bone defect models?

BACKGROUND: In revision surgery with significant segmental acetabular defects, adequate implant selection and fixation methods are critical in determining successful bony ingrowth. Commercially available total hip prosthesis manufacturers generally offer additional multi-hole options of acetabular shells with identical designs for use in revision THAs where screw holes configurations vary from product to product. This study aims to compare the mechanical stability of the two types of acetabular screw constructs for the fixation of acetabular components: spread-out and pelvic brim-focused configurations. METHODS: We prepared 40 synthetic bone models of the male pelvis. In half of the samples with acetabular defects, identical curvilinear bone defects were manually created using an oscillating electrical saw. On the right side, multi-hole-cups in which the direction of the screw holes are centered on the pelvic brim (brim-focused) and, on the left side, multi-hole-cups with the direction of the screw hole spread throughout the acetabulum (spread-out) were implanted into the pelvic synthetic bones. Coronal lever-out and axial torsion tests were performed with a testing machine, measuring load versus displacement. RESULTS: The average torsional strengths were significantly higher in the spread-out group over the brim-focused group regardless of the presence of the segmental defect of the acetabulum (p < 0.001). But for the lever-out strength, the spread-out group exhibited significantly higher average strength over the brim-focused group for the intact acetabulum (p = 0.004), whereas the results were reversed in the brim-focused group when the defects were generated (p < 0.001). The presence of acetabular defects reduced the average torsional strengths of the two groups by 68.66% versus 70.86%. In comparison, the decrease in the average lever-out strength was less significant for the brim-focused group than the spread-out group (19.87% vs. 34.25%) (p < 0.001). CONCLUSION: Constructs of multi-hole acetabular cups with the spread-out screw holes configuration exhibited statistically better axial torsional strength and coronal lever-out strength. With the presence of posterior segmental bone defects, the spread-out constructs demonstrated significantly better tolerance to axial torsional strength. Still, they exhibited inverted results of higher lever-out strength in the pelvic brim-focused constructs.

Weight-Based Bisphosphonate Administration for Multiple Myeloma Patients and the Risks of Skeletal Complications.

High-dose bisphosphonate for multiple myeloma patients might elevate risks of skeletal complications earlier than general expectations. This study aims to find incidences of atypical femoral fracture (AFF) and medication-related osteonecrosis of the jaw (MRONJ), elucidate their risk factors, and suggest cut-off values for the safer dosing of high-dose bisphosphonate treatment. By using the clinical data warehouse of a single institute, retrospective cohort data of multiple myeloma-diagnosed patients with high-dose bisphosphonate (pamidronate or zoledronate) treatment from 2009 to 2019 was extracted. Among 644 patients, the incidence of prominent AFF requiring surgery was 0.93% (6/644) and MRONJ was diagnosed in 11.8% (76/644) of the study population. For both AFF and MRONJ, the total potency-weighted sum of total dose per body weight (OR = 1.010, p = 0.005) were significant on logistic regression. Cutoffs of the potency-weighted total dose (mg) per body weight (kg) for AFF and MRONJ were 77.00 and 57.70 mg/kg, respectively. After roughly one year of treatment with high-dose zoledronate (about four years for pamidronate), an earlier thorough re-evaluation of skeletal complications should be taken. Body weight adjustments for accumulative dose calculation in terms of permissible dosing should be taken into consideration.

Comparison of tumor regression grade and clinical stage based on MRI image as a selection criterion for non-radical management after concurrent chemoradiotherapy in locally advanced rectal cancer: a multicenter, retrospective, cross-sectional study.

PURPOSE: There has been no comparative study on the clinical value of magnetic resonance tumor regression grade (mrTRG)1-2 and ycT0-1N0 for the prediction of ypT0-1N0 after concurrent chemoradiotherapy (CCRT) for rectal cancer. We compared the diagnostic performance between mrTRG1-2 and ycT0-1N0 for predicting ypT0-1N0 as a selection criterion for non-radical management after CCRT in locally advanced rectal cancer. METHODS: This retrospective study enrolled 291 patients from three referral hospitals between January 2018 and March 2020. The diagnostic performance of ycT0-1N0 and mrTRG1-2 for the prediction of ypT0-1N0 was compared in terms of sensitivity, specificity, positive-predictive value, negative-predictive value, and area under the curve (AUC). RESULTS: Sixty-eight patients (23.4%) achieved ypT0-1N0. Nineteen patients (6.5%) had ycT0-1N0, and 91 patients (31.2%) had mrTRG1-2. For predicting ypT0-1N0, ycT0-1N0 had a sensitivity of 16.2% (95% confidence interval [CI]: 8.36‒27.10) and positive-predictive value of 57.9% (95% CI: 36.57‒76.63), while mrTRG1-2 had a sensitivity of 58.8% (95% CI: 46.23‒70.63) and positive-predictive value of 44.0% (95% CI: 36.46‒51.74). When predicting ypT0-1N0, mrTRG1-2 showed a higher AUC (0.680, 95% CI: 0.604‒0.756) than ycT0-1N0 (0.563, 95% CI: 0.481‒0.645) (P < 0.001). CONCLUSION: mrTRG1-2 might be a better indicator than ycT0-1N0 for the selection of non-radical management of advanced rectal cancer post-CCRT. However, additional diagnostic tools are required for predicting ypT0-1N0 because mrTRG1-2 or yc stage on MRI has insufficient evidence for diagnosing ypT0-1N0.

Modified hybrid cementing technique reduces stem tip pain and improves patient's satisfaction after revision total knee arthroplasty.

BACKGROUND: There have been no studies comparing patient-reported outcome measures including end-of-stem tip pain and patient satisfaction based on the use of cementing techniques in revision total knee arthroplasty (TKA). The purpose of this study was to compare end-of-stem tip pain and PROMs with hybrid and modified hybrid cementing techniques in revision TKAs. METHOD: Sixty-two cases of revision TKA performed by a single surgeon were divided into two groups based on the cementing technique with a minimum follow-up of 2 years. Two types of cementing technique for femoral and tibial stems were used as follows: (1) a hybrid cementing technique (33 cases), in which cement was applied immediately distal to the modular junction of the stem and the component while the distal stem was press-fitted into the diaphysis without using cement; and (2) a modified hybrid cementing technique (29 cases), in which cement was applied to the tip of femoral and tibial stems. The thigh and shin were assessed for the end-of-stem tip pain. Patient satisfaction was evaluated based on the satisfaction items of New Knee Society Score. RESULTS: Modified hybrid cementing significantly lowered the percentage of patients manifesting shin pain (3.4% vs. 24.2%, p = 0.029). Patients treated with the modified hybrid cementing technique showed a higher satisfaction rate (p = 0.003). Multivariate logistic regression analysis showed an increase in the odds of satisfaction 32.686-fold (p = 0.004) in patients without pain at the end-of-stem tip in the shin and 9.261-fold (p = 0.027) in patients treated with the modified hybrid cementing technique. CONCLUSION: The modified hybrid cementing technique for fixation of long-stem in revision TKAs reduced the end-of-stem tip pain in the shin, leading to significantly higher satisfaction compared with the hybrid cementing technique after revision TKA. LEVEL OF EVIDENCE: Level III.

Relationship between iliac screw loosening and proximal junctional kyphosis after long thoracolumbar instrumented fusion for adult spinal deformity.

PURPOSE: Authors assumed that the stability of iliac screw (IS) fixation could affect the development of proximal junctional kyphosis (PJK). The purpose of this study was to analyze the relationship between IS loosening and PJK after long fusion surgery for adult spinal deformity (ASD). METHODS: Sixty-eight ASD patients (6 males, 62 females; mean age, 68.1 years) who underwent long fusion surgery with IS fixation were reviewed. The incidence and risk factors of IS loosening were investigated. The relationship between IS loosening and PJK was also analyzed. RESULTS: IS loosening and PJK appeared in 33 and 19 patients, respectively. The median time for IS loosening and PJK to develop was 6.0 months (range 1.3-59.2) and 9.1 months (range 1.3-73.2), respectively. PJK developed in patients without IS loosening more frequently than in patients with IS loosening. PJK did not develop in 28 patients who presented with IS loosening first. IS loosening developed 5 months postoperatively in those 28 patients, whereas IS loosening was present 11 months postoperatively in 4 patients who presented with PJK first. Preoperative PT (OR = 1.091) and IS loosening (OR = 0.343) were significantly related with the development of PJK. IS loosening was significantly associated with postoperative PI-LL > 10° (OR = 0.957), postoperative SVA (OR = 1.023), and postoperative PT (OR = 1.072). CONCLUSION: Postoperative sagittal malalignment should be avoided to prevent IS loosening and PJK. IS loosening occurred earlier than PJK and seemed to affect the development of PJK. This relationship supports the hypothesis that distal stability of long constructs may increase proximal junctional stress. LEVEL OF EVIDENCE: III. These slides can be retrieved under Electronic Supplementary Material.

Ten-year experience of esophageal endoscopic submucosal dissection of superficial esophageal neoplasms in a single center.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) of a superficial esophageal neoplasm (SEN) is a technically difficult procedure. We investigated the clinical outcomes of ESD to determine its feasibility and effectiveness for the treatment of SEN. METHODS: Patients who underwent ESD for SEN between August 2005 and June 2014 were eligible for this study. The clinical features of patients and tumors, histopathologic characteristics, adverse events, results of endoscopic resection, and survival were investigated. RESULTS: ESD was performed in 225 patients with 261 lesions, including 70 cases (26.8%) of dysplasias and 191 cases (73.2%) of squamous cell carcinomas. The median age was 65 years (range, 44 to 86), and the male to female ratio was 21.5:1. Median tumor size was 37 mm (range, 5 to 85) and median procedure time was 45 minutes (range, 9 to 160). En bloc resection was performed in 245 of 261 lesions (93.9%), with complete resection in 234 lesions (89.7%) and curative resection in 201 lesions (77.0%). Adverse events occurred in 33 cases (12.6%), including bleeding (1.5%), perforation (4.6%), and stricture (6.5%). During a median follow-up period of 35.0 months (interquartile range, 18 to 62), none of the patients showed local recurrence. The 5-year overall and disease-specific survival rates were 89.7% and 100%, respectively. CONCLUSIONS: ESD is a feasible and effective procedure for the treatment of SEN based on our 10-year experience, which showed favorable outcomes.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Proteomic analysis of SP600125-controlled TrkA-dependent targets in SK-N-MC neuroblastoma cells: inhibition of TrkA activity by SP600125.

The c-Jun N-terminal kinase (JNK) is well known to play an important role in cell death signaling of the p75 neurotrophin receptor. However, little has been studied about a role of JNK in the signaling pathways of the tropomyosin-related kinase A (TrkA) neurotrophin receptor. In this study, we investigated JNK inhibitor SP600125-controlled TrkA-dependent targets by proteomic analysis to better understand an involvement of JNK in TrkA-mediated signaling pathways. PDQuest image analysis and protein identification results showed that hnRNP C1/C2, α-tubulin, ß-tubulin homolog, actin homolog, and eIF-5A-1 protein spots were upregulated by ectopic expression of TrkA, whereas α-enolase, peroxiredoxin-6, PROS-27, HSP70, PP1-gamma, and PDH E1-alpha were downregulated by TrkA, and these TrkA-dependent upregulation and downregulation were significantly suppressed by SP600125. Notably, TrkA largely affected certain PTM(s) but not total protein amounts of the SP600125-controlled TrkA-dependent targets. Moreover, SP600125 strongly suppressed TrkA-mediated tyrosine phosphorylation signaling pathways as well as JNK signaling, indicating that SP600125 could function as a TrkA inhibitor. Taken together, our results suggest that TrkA could play an important role in the cytoskeleton, cell death, cellular processing, and glucose metabolism through activation or inactivation of the SP600125-controlled TrkA-dependent targets.

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.

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.