• Journal of Korean Neurosurgical Society
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• v.57 no.1
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• pp.36-41
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• 2015

Objective : To investigate the causes for failed anterior cervical surgery and the outcomes of secondary laminoplasty. Methods : Seventeen patients failed anterior multilevel cervical surgery and the following conservative treatments between Feb 2003 and May 2011 underwent secondary laminoplasty. Outcomes were evaluated by the Japanese Orthopaedic Association (JOA) Scale and visual analogue scale (VAS) before the secondary surgery, at 1 week, 2 months, 6 months, and the final visit. Cervical alignment, causes for revision and complications were also assessed. Results : With a mean follow-up of $29.7{\pm}12.1$ months, JOA score, recovery rate and excellent to good rate improved significantly at 2 months (p< 0.05) and maintained thereafter (p>0.05). Mean VAS score decreased postoperatively (p<0.05). Lordotic angle maintained during the entire follow up (p>0.05). The causes for secondary surgery were inappropriate approach in 3 patients, insufficient decompression in 4 patients, adjacent degeneration in 2 patients, and disease progression in 8 patients. Complications included one case of C5 palsy, axial pain and cerebrospinal fluid leakage, respectively. Conclusion : Laminoplasty has satisfactory results in failed multilevel anterior surgery, with a low incidence of complications.

• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.285-292
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• 2015

LIM kinases belong to the serine/Threonine kinase family. The members of the LIM kinase (LIMK) family include LIMK 1 and 2 which are involved in the regulation of actin polymerisation and microtubule disassembly. LIMK1 was shown to be involved in cancer metastasis, while LIMK2 activation promotes cells cycle progression. Since LIMK2 plays a vital role in many disease conditions such as pulmonary hypertension, cancer and viral diseases, and till date there are not much selective inhibitors been reported, LIMK2 becomes an interesting therapeutic target among the kinases. 3D QSAR study was carried out on a series of pyrrolopyrimidines based derivatives as LIMK2 inhibitors. A reasonable CoMFA ($q^2$=0.888; ONC=3; $r^2$=0.974) with good statistical values was developed. The developed model was validated using 1000 runs of boostrapping and was found to be predictable. The results of CoMFA contour map analysis suggested that the bulky substitution at $R_4$ and $R_5$ position are highly desirable to increase the activity. Similarly, positive substitution at $R_3$ position is also required to increase the activity. It is also noted that bulky substitution at $R_1$ position must be avoided. Our results could provide valuable information to enhance the activity of the LIMK2 inhibitors and to design potent pyrrolopyrimidines derivatives.

• Journal of Veterinary Clinics
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• v.35 no.5
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• pp.178-183
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• 2018

The object of this study was to compare magnetic resonance imaging (MRI) findings and neurological signs in canine brain diseases. Brain diseases can cause severe neurological deficits and may be life-threatening. The antemortem diagnosis of the brain diseases is difficult for the clinician, since definitive diagnosis is based upon histopathological confirmation. Brain diseases are often associated with specific clinical signs, signalment, progression, and location. Accurate lesion localization through neurological examination and MRI findings is helpful for developing a differential diagnosis. A retrospective study was performed to compare the neurological examination of dogs with suspected brain disease to the MRI findings. Based on this study, neurological examination is a reliable way to localize most brain lesions. Postural reaction deficits do not provide sufficient information to localize lesions. Additionally, not all brain lesions present clinical signs and inflammatory lesions may cause no detectable abnormalities on MRI. Therefore, in clinical practice, a combination of neurological examination and MRI findings recommended for accurate brain lesion localization.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.197-204
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• 2012

Purpose: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Materials and Methods: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were reevaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and ${\beta}$-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. Results: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and ${\beta}$-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. Conclusion: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and ${\beta}$-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.134-142
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• 2020

Colon cancer is one of the most common malignant tumors, but there are still a few validated biomarkers of colon cancer. Exosome-mediated microRNAs (miRNAs) have been recognized as potential biomarkers in cancers, and miRNAs can regulate a variety of genes. Recently, Fusobacterium nucleatum was discovered in the tissues of human colon cancer patients. Its role in colon cancer was highlighted. F. nucleatum may contribute to the progression of colon cancer through the mechanism of exosome-mediated miRNAs transfer. However, the exosomal miRNAs regulation mechanism by F. nucleatum in colon cancer is not well known. Thus, we performed next-generation sequencing to investigate the overall pattern of exosomal miRNAs expression in the colon cancer cell culture supernatant. We have confirmed the alterations of various exosomal miRNAs. In addition, to investigate the function of exosomal miRNAs, a Kyoto Encyclopedia of Genes and Genomes analysis was performed on the target genes of changed miRNAs. Potential target genes were associated with a variety of signaling pathways, and one of these pathways was related to colorectal cancer. These findings suggested that F. nucleatum can alter exosomal miRNAs released from colorectal cancer cells. Furthermore, exosomal miRNAs altered by F. nucleatum could be potential biomarkers for the diagnosis and therapy of colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9171-9176
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• 2014

Aim: P53, the most commonly mutated tumor suppressor gene in all types of human cancer, is involved in cell cycle arrest and control of apoptosis. Although p53 contains several polymorphic sites, the codon 72 polymorphism is by far more common. There are divergent reports but many studies suggest p53 pro/pro SNP may be associated with susceptibility to developing various cancers in different regions of the world. The present study aimed to find any correlation between H. pylori infection and progression of carcinogenesis, by studying apoptosis and the p53 gene in gastric biopsies from north Indian population. Materials and Methods: A total of 921 biopsies were collected and tested for prevalence of H. pylori by rapid urease test (RUT), imprint cytology and histology. Apoptosis was studied by the TUNEL method. Analysis of p53 gene polymorphism at codon 72 was accomplished by PCR using restriction enzyme BstU1. Observation: Out of 921 samples tested 56.7% (543) were H. pylori positive by the three techniques. The mean apoptotic index (AI) in the normal group was 2.12, while gastritis had the maximum 4.24 followed by gastric ulcer 2.28, gastropathy 2.22 and duodenal ulcer 2.08. Mean AI in cases with gastric cancer (1.72) was less than the normal group. The analysis of p53 72 SNP revealed that p53 (Arg/Arg), (Pro /Arg) variant are higher (40.59% & 33.66%) as compared to p53 pro/pro variant (25.74%) inthe healthy population. Conclusions: The North Indian population harbors Arg or Pro/Arg SNP that is capable of withstanding stress conditions; this may be the reason of low incidence of gastric disease in spite of high infection with H. pylori. There was no significant association with H. pylori infection and AI. However, there is increased apoptosis in gastritis which may occur independent of H. pylori or p53 polymorphism.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4515-4520
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• 2015

GELOX (gemcitabine, oxaliplatin and L-asparaginase) regimen showed an impressive result in our previous study, but the effect of this new regimen is still dissatisfying for some patients, so it is necessary to identify which patients will benefit from this regimen. A total of fifty-one cases with nasal natural killer/T-cell lymphoma receiving initial GELOX chemotherapy were enrolled in this study. The ki-67 expression detected by immunohistochemistry (IHC) in the specimens ranged from 10% to 90%, with a median value of 70%, so cases higher than the median value (${\geq}70%$) were defined as high ki-67 expression, and the others were designated as low ki-67 expression. The response rate had no statistical difference between low ki-67 expression group and high ki-67 expression group (P=0.291) though the value in the former group was relatively high. After a median follow-up of 18.03 months, the 3-year progression-free survival (PFS) for patients with low ki-67 expression was significantly higher than those with high ki-67 expression (83.8% vs. 47.9%, P=0.038). In the stage I/II subgroup, 3-year PFS and overall survival (OS) were statistically higher in the patients with low ki-67 expression than those with high ki-67 expression. Multivariate analysis revealed high ki-67 expression was an independent prognostic factor for PFS. These results suggest that low ki-67 expression can predict a good response of GELOX in these patients, and the combination of ki-67 expression and early stage is helpful to identify an excellent prognosis subgroup from patients receiving GELOX in this disease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8461-8465
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• 2016

Gastric cancer (GC) as the fourth most common cause of malignancies shows high rate of morbidity appropriating the second leading cause of cancer-related death worldwide. Developmental pluripotency associated-2 (DPPA2), cancer-testis antigen (CT100), is commonly expressed only in the human germ line and pluripotent embryonic cells but it is also present in a significant subset of malignant tumors. To investigate whether or not DPPA2 expression is recalled in GC, our aim in this study was to elucidate DPPA2 protein expression in gastric cancer. Fifty five GC tumor and their related margin normal tissues were recruited to evaluate DPPA2 protein expression and its probable associations with different clinicopathological features of the patients. DPPA2 was overexpressed in GC cases compared with normal tissues (P < .005). While DPPA2 expression was detected in all GC samples, its high expression was found in 23 of 55 tumor tissues (41.8%). Interestingly, 50 of 55 normal samples (90.9%) were negative for DPPA2 protein expression and remained 5 samples showed very low expression of DPPA2. DPPA2 protein expression in GC was significantly correlated with lymph node metastasis (p = 0.012). The clinical relevance of DPPA2 in GC illustrated that high level expression of this protein was associated with lymph node metastasis supporting this hypothesis that alteration in DPPA2 was associated with aggressiveness of gastric cancer and may be an early event in progression of the disease. DPPA2 may be introduced as a new marker for invasive and metastatic GCs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4691-4698
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• 2015

Background: The tumor suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. However, available results for the prognostic value of PTEN expression in patients with cancer remain controversial. Therefore, a meta-analysis of published studies investigating this issue was performed. Materials and Methods: A literature search via PubMed and EMBASE databases was conducted. Statistical analysis was performed by using the STATA 12.0 (STATA Corp., College, TX). Data from eligible studies were extracted and included into the meta-analysis using a random effects model. Results: A total of 3,810 patients from 27 studies were included in the meta-analysis, 22 investigating the relationship between PTEN expression and overall survival (OS) using univariate analysis, and nine with multivariate analysis. The pooled hazard ratio (HR) for OS was 1.64 (95% confidence interval (CI): 1.32-2.05) by univariate analysis and 1.56 (95% CI: 1.20-2.03) by multivariate analysis. In addition, eight papers including two disease-free-survival analyses (DFSs), four relapse-free-survival analyses (RFSs), three progression-free-survival analyses (PFSs) and one metastasis-free-survival analysis (MFS) reported the effect of PTEN on survival. The results showed that loss of PTEN expression was significant correlated with poor prognosis, with a combined HR of 1.74 (95% CI: 1.24-2.44). Furthermore, in the stratified analysis by the year of publication, ethnicity, cancer type, method, cut-off value, median follow-up time and neoadjuvant therapy in which the study was conducted, we found that the ethnicity, cancer type, method, median follow-up time and neoadjuvant therapy are associated with prognosis. Conclusions: Our study shows that negative or loss of expression of PTEN is associated with worse prognosis in patients with cancer. However, adequately designed prospective studies need to be performed for confirmation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4117-4123
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• 2014

Background: To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). Materials and Methods: The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. Results: There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). Conclusions: ERCC1 was identified as poor prognostic factor in patients with MPM.