• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.30-35
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• 2006

Tissue-type plasminogen activator (t-PA) is a multidomain serine protease containing two kringle domains, TK1-2. Previously, Pichia-derived recombinant human TK1-2 has been reported as an angiogenesis inhibitor although t-PA plays an important role in endothelial and tumor cell invasion. In this work, in order to improve in vivo efficacy of TK1-2 through elimination of immune reactivity, we mutated wild type TK1-2 into non-glycosylated form (NE-TK1-2) and examined whether it retains anti-angiogenic activity. The plasmid expressing NE-TK1-2 was constructed by replacing $Asn^{l17}\;and\;Asn^{184}$ with glutamic acid residues. After expression in Pichia pastoris, the secreted protein was purified from the culture broth using S-sepharose and UNO S1-FPLC column. The mass spectrum of NE-TK1-2 showed closely neighboring two peaks, 19631.87 and 19,835.44 Da, and it migrated as one band in SDS-PAGE. The patterns of CD-spectra of these two proteins were almost identical. Functionally, purified NE-TK1-2 was shown to inhibit endothelial cell migration in response to bFGF stimulation at the almost same level as wild type TK1-2. Therefore, the results suggest that non-glycosylated NETK1-2 can be developed as an effective anti-angiogenic and anti-tumor agent devoid of immune reactivity.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.4
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• pp.180-188
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• 2009

Plakoglobin (PKG) is a protein linking cadherin adhesion receptors to the actin cytoskeleton and its overexpression has been known to suppress cell proliferation and tumorigenesis in thyroid cancer. We investigated the effect of 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, on the methylation status of the promoter and the expression of the plakoglobin gene in a thyroid carcinoma cell line (ARO) and papillary thyroid carceinoma. In cultures of ARO cell line incubated without 5-Aza-2'-deoxycytidine (5-Aza-CdR), five of the fifteen CpG sites in the promoter spanning -225 and -54 were methylated at 4.2 - 12.5%. When the cells were treated with 5-Aza-CdR, all the methylated CpG sites were induced to be demethylated except one. In addition, a new methylation at one CpG site, CpG4, was identified at level of 12.0%. The expression level of PKG decreased approximately 10-fold in the 5-Aza-CdR treated cells compared to untreated cells. Different pattern of promoter methylation and expression of PKG was also observed in the tissue samples. CpG10 and CpG12 sites were methylated at 9.0-27.0% in normal tissues. However, in cancer tissues, CpG5 and CpG10 sites were methylated at 10.0-22.0%. Three of ten normal thyroid tissue samples and one of thirteen papillary carcinoma tumor samples showed increased PKG mRNA expression level. PKG protein expression analyzed by the immunohistochemical staining showed higher expression in the tumor compared with normal.

• Journal of Gastric Cancer
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• v.16 no.1
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• pp.21-27
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• 2016

Purpose: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions: We suggested that TLE1 expression is a good prognostic indicator in GCs.

• The Korean Journal of Nuclear Medicine
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• v.34 no.4
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• pp.265-275
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• 2000

The thyroid gland is an interesting endocrine organ where a spectrum of tumors with different behavior arise. At one end of spectrum there is differentiated thyroid carcinoma (DTC) with excellent prognosis, whereas at the other end of the spectrum is anaplastic thyroid cancer which has universally poor outcome. Radioiodine (I-131) therapy has been in use for the treatment of thyroid diseases since 1946. It was introduced by Seidlin et al. 1) Although the use of I-131 has been vouge for a long time, its use in therapy for well differentiated thyroid cancer is still controversial 2). This is because, thyroid cancers (TC) are generally slow growing tumors, with low mortality and normal spans of survival. To record recurrence and mortality, long term follow up studies over a period of two to three decades are needed to establish definite conclusions on the acceptable mode of treatment The incidence of the disease being very low a large number of cases needed to establish a meaningful statistical data is lacking as most published reports feat with small series. Here again in the problem encountered are the differing protocols for treatment with I-131, the indications for treatment which may include or exclude ablation of residual thyroid tissue, cervical nodal and distal metastases. The dosage of I-131 used for ablation of residual thyroid tissue and metastatic disease also vary. The most reliable conclusion regarding I-131 treatment are obtained from studies reported on a large series of patients followed over a period of 2 decades or more from a single institute with a more or less unchanged protocol of management.

• BMB Reports
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• v.54 no.10
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• pp.497-504
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• 2021

EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.918-926
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• 2022

Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.132-136
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• 2021

Local anesthetic (LA) injection outside the sheath in epineural or paraneural connective tissue is considered safe practice among regional anesthesiologists. There is limited evidence as to whether neurological complications occur if LA is injected inside the sheath (subepineural - intraneural). We performed ultrasound guided injections at the level of undivided sciatic nerve in four amputated lower limbs. In two specimens, LA was injected in epineural connective tissue (paraneural tissue) and in another two specimens by penetrating the outer nerve sheath (hyperechoic epineurium). Ultrasonography demonstrated an increase in the size of nerve and macroscopic findings revealed fascicular tracings with sub-epineural injections. Limbs were sent for histological analysis in formalin containers. Pathologist performed the analysis which demonstrated an intact perineurium and a breach in the epineurium. We conclude that sub-epineural injections are unsafe and injection should be done in paraneural tissue to ensure safety and avoid unwanted neurological sequelae after the block.

• Archives of Plastic Surgery
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• v.39 no.5
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• pp.518-521
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• 2012

Background Skin cancer is the most common malignant tumor in humans. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common types of skin cancers. When skin cancer is clinically suspected, preoperative biopsies are recommended for a definite diagnosis. However, despite a concern over potential increased risk of metastasis associated with mechanical manipulation, there have been few investigations into whether a preoperative biopsy affected the recurrence of BCC and SCC. Methods Primary BCC or SCC patients who underwent standard surgical excision from 1991 to 2010 were reviewed and a retrospective analysis was performed. Ultimately, 45 BCC patients and 54 SCC patients, who did not meet the exclusion criteria, were analyzed. To identify whether a preoperative biopsy affected the recurrence of BCC and SCC, the recurrence rates of each with and without biopsy were compared. Results Preoperative biopsy had no statistically significant effect on recurrence (BCC, P=0.8680; SCC, P=0.7520). Also, there was no statistical significance between the interval from initial biopsy to first operation and recurrence (BCC, P=0.2329; SCC, P=0.7140). Even though there was no statistical significance, the mean interval from the biopsy to the operation among the BCC patients who underwent preoperative biopsy was 9.2 months in those who had recurrence and 2.0 months in those who had no recurrence. Conclusions There was no statistically significant relationship between preoperative biopsy and recurrence of BCC and SCC. However, there was a tendency toward recurrence in patients with a longer interval between the biopsy and the corrective operation in BCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.1011-1014
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• 2014

Background: Soft tissue sarcomas (STS) represent 1% of all malignant lesions. In this study the authors analyzed the incidence of STS in Vojvodina (the north region of Serbia) in the period from 1985 to 2009. A number of studies conducted worldwide indicate that STS incidence rates are tending to increase. Materials and Methods: On the basis of data from the Cancer Registry of Vojvodina, age standardized STS incidence rates were established as well as their linear trend, with data on histological structure, age, gender and STS distribution at specific locations. Results: The total number of registered patients was 1,308. Average age standardized rate was 1.90/100,000 per year. The investigated period showed a slight increase in the incidence rate (average annual percent increase=0.77%). The most frequent histological type was sarcoma not otherwise specified-NOS (27%), followed by leiomyosarcoma (21%), liposarcoma (14%), rhabdomyosarcoma (11%) and malignant fibrous histiocytoma (9%). The male/female ratio was 0.73:1. Every fifth patient was younger than 39. Conclusions: Comparison among eight international STS epidemiology studies show that the incidence rate range is between 1.4/100,000-5.0/100,000, though our finding is closer to the lower limit. Furthermore, the incidence rate increase was lower than that characteristic for the half of the analyzed studies. A partial explanation for that should be looked for among changes in diagnostic criteria and STS classifications.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8579-8587
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• 2016

Background: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), with the inflammatory markers nuclear factor kappa B/p65 (NF-${\kappa}B$/P65) and interleukin-1 beta (IL-$1{\beta}$) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-${\kappa}B$/P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-$1{\alpha}$ and IL-$1{\beta}$ were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma ($1.47{\pm}0.31$ and $184.98{\pm}18.18$, respectively) compared to low grade carcinoma ($1.21{\pm}0.32$ and $171.76{\pm}7.58$, respectively) and controls ($0.70{\pm}0.02$ and $65.34{\pm}6.41$, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-$1{\alpha}$ and IL-$1{\beta}$ as well as NF-${\kappa}B$/P65 DNA binding activity were significantly higher in high grade breast carcinoma ($148.54{\pm}14.20$, $0.79{\pm}0.03$ and $247.13{\pm}44.35$ respectively) than their values in low grade carcinoma ( $139.14{\pm}5.83$, $0.34{\pm}0.02$ and $184.23{\pm}37.75$, respectively) and controls ($33.95{\pm}3.11$, $0.11{\pm}0.02$ and $7.83{\pm}0.92$, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-$1{\alpha}$ could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-$1{\beta}$ and NF-${\kappa}B$/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.