• Journal of Life Science
• /
• v.30 no.5
• /
• pp.483-490
• /
• 2020

The ubiquitin system uses ligases and deubiquitinases (DUBs) to regulate ubiquitin position on protein substrates and is involved in many biological processes which determine stability, activity, and interaction of the target substrate. DUBs are classified in six groups according to catalytic domain, namely ubiquitin-specific proteases (USPs); ubiquitin C-terminal hydrolases (UCHs); ovarian tumor proteases (OTUs); Machado Joseph Disease proteases (MJDs); motif interacting with Ub (MIU)-containing novel DUB family (MINDY); and Jab1/MPN/MOV34 metalloenzymes (JAMMs). Otubain 1 (OTUB1) is a DUB in the OTU family which possesses both canonical and non-canonical activity and can regulate multiple cellular signaling pathways. In this review, we describe the function of OTUB1 through regulation of its canonical and non-canonical activities in multiple specifically cancer-associated pathways. The canonical activity of OTUB1 inhibits protein ubiquitination by cleaving Lys48 linkages while its non-canonical activity prevents ubiquitin transfer onto target proteins through binding to E2-conjugating enzymes, resulting in the induction of protein deubiquitination. OTUB1 can therefore canonically and non-canonically promote tumor cell proliferation, invasion, and drug resistance through regulating FOXM1, ERα, KRAS, p53, and mTORC1. Moreover, clinical research has demonstrated that OTUB1 overexpresses with high metastasis in many tumor types including breast, ovarian, esophageal squamous, and glioma. Therefore, OTUB1 has been suggested as a diagnosis marker and potential therapeutic target for oncotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1115-1118
• /
• 2016

Background: There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. Materials and Methods: This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis. Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. Results: Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ${\leq}7.4ng/ml$ had the highest diagnostic strength to predict successful ablation in all patients. Conclusions: We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline $sTg{\leq}7.4ng/ml$ is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1519-1529
• /
• 2016

Background: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9) are key molecules that play roles in tumor growth, invasion, tissue remodeling, metastasis and stem-cell regulation by digesting extracellular matrix barriers. MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in hematological malignancies, a paucity of data is available to resolve the function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs) and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Objectives: The present study aimed to investigate mRNA expression and gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C; rs8179090) in MDS and AML. Results: The study covered cases of confirmed MDS (n=50), AML (n=32) and healthy controls (n=110). MMP-9 mRNA expression revealed 2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70% blasts). Secretion of gelatinase-B also revealed the MMP-9 mRNA expression and ELISA data also supported these data. We noted that those patients having more blast crises presented with more secretion of MMP-9 and its mRNA expression. In contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were 1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS, while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML. Conclusions: In view of our results, MMP-9 revealed synergistic secretion and expression in blast crises of MDS and AML with 'gene' polymorphic effects and is significantly associated with increased risk with tobacco, cigarette and environmental exposure. Release and secretion of these enzymes may influence hematopoietic cell behavior and may be important in the clinical point of view. It may offer valuable tools for diagnosis and prognosis, as well as possible targets for the treatments.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6401-6406
• /
• 2015

Background: It is sometimes difficult to assess patients who have multiple hilar and mediastinal lymph nodes (MHMLN) with FDG accumulation in PET-CT. Since it is uncertain whether diffusion-weighted magnetic resonance imaging (DWI) is useful in the assessment of such patients, its diagnostic performance was assessed. Materials and Methods: Twenty-three patients who had three or more stations of hilar and mediastinal lymph nodes with SUVmax of 3 or more in PET-CT were included in this study. Results: For diagnosis of disease, there were 20 malignancies (lung cancers 17, malignant lymphomas 2 and metastatic lung tumor 1), and 3 benign cases (sarcoidosis 2 and benign disease 1). For diagnosis of lymph nodes, there were 7 malignancies (metastasis of lung cancer 7 and malignant lymphoma 1) and 16 benign lymphadenopathies (pneumoconiosis/silicosis 7, sarcoidosis 4, benign disease 4, and atypical lymphocyte infiltration 1). The ADC value ($1.57{\pm}0.29{\times}10^{-3}mm^2/sec$) of malignant MHMLN was significantly lower than that ($1.99{\pm}0.24{\times}10^{-3}mm^2/sec$) of benign MHMLN (P=0.0437). However, the SUVmax was not significantly higher ($10.0{\pm}7.34$ as compared to $6.38{\pm}4.31$) (P=0.15). The sensitivity (86%) by PET-CT was not significantly higher than that (71%) by DWI for malignant MHMLN (P=1.0). The specificity (100%) by DWI was significantly higher than that (31%) for benign MHMLN (P=0.0098). Furthermore, the accuracy (91%) with DWI was significantly higher than that (48%) with PET-CT for MHMLN (P=0.0129). Conclusions: Evaluation by DWI for patients with MHMLN with FDG accumulation is useful for distinguishing benign from malignant conditions.

• Advances in Traditional Medicine
• /
• v.1 no.1
• /
• pp.8-27
• /
• 2000

Components of extracellular matrix and the matrix-degrading enzymes are some of the key regulators of tumor metastasis and angiogenesis. Hyaluronic acid (HA), a matrix glycosaminoglycan, is known to promote tumor adhesion and migration, and its small fragments are angiogenic. Until now, we have compared levels of hyaluronidase, an enzyme that degrade HA, in normal adult prostate, benign prostate hyperplasia and prostate cancer tissues and in conditioned media from epithelial explant cultures, using a substrate (HA)-gel assay and ELISA-like assay (Kim et al., unpublished results). The present review described an overall characterization of hyaluronidases and its application to human diseases. The hyaluronidases are a family of enzymes that have, until recently, deed thorough explication. The substrate for these enzymes, hyaluronan, is becoming increasingly important, recognized now as a major participant in basic processes such as cell motility, wound healing, embryogenesis, and implicated in cancer progression. And in those lower life forms that torment human beings, hyaluronidase is associated with mechanisms of entry and spread, e.g. as a virulence factor for bacteria, for tissue dissection in gas gangrene, as a means of treponema spread in syphilis, and for penetration of skin and gut by nematode parasites. Hyaluronidase also comprises a component of the venom of a wide variety of organisms, including bees, wasps, hornets, spiders, scorpions, sh, snakes and lizards. Of particular interest is the homology between some of these venom hyaluronidases and the enzyme found in the plasma membrane of mammalian spermatozoa, attesting to the ancient nature of the conserved sequence, a 36% identity in a 300 amino acid stretch of the enzyme protein. Clearly, hyaluronidase is of biological interest, being involved in the pathophysiology of so many important' human disorders. Greater effort should be made in studying this family of enzymes that have, until recently, been overlooked. Also, oriental medical application of the hyaluronidase will be discussed with respect to inhibition and suppression of inflammation and malignacy.

• Journal of Chest Surgery
• /
• v.31 no.2
• /
• pp.212-215
• /
• 1998

Pulmonary mucinous cystic tumor of borderline malignancy is very rare and distinguished from bronchogenic cyst or adenocarcinoma of bronchoalveolar type. We present the case of a 63-year-old woman with a right lower lobe mass, found by chest radiographs. The preoperative diagnosis was made as bronchoalveolar cancer by percutaneous needle aspiration of mass. Right lower lobectomy and lymph node dissections were performed. The lobectomy specimen contained variable sized multilocular cystic mucous masses, filled with mucus. Microscopically, the cystic masses are lined with tall columnar mucinous epithelium but some area contains focal cellular atypism and bronchoalveolar cancer like foci. This foci are lack of cellular atypism consistent with bronchoalveolar cancer cell. After lobectomy the patient has remained free from recurrence and distant metastasis for following 12 months period. Pulmonary mucinous cystic tumor of borderline malignancy appears to have a favorable prognosis and should be distinguished from other lung neoplasms.

• The Journal of the Korean bone and joint tumor society
• /
• v.11 no.1
• /
• pp.32-39
• /
• 2005

Introduction: Currently, F-18 fluorodeoxyglucose positron emission tomography scans (FDG-PET) has been investigated in soft tissue tumor especially for tumor detection and noninvasive grading. However, the validity and the efficacy of FDG-PET are still unclear in clinical evaluation. The purpose of this study is to determine the efficacy of FDG-PET in compared to conventional diagnostic imaging studies currently used in the soft tissue tumor. Methods: Between March 2001 and March 2002, 29 patients (sixteen males, thirteen females, mean age, 47 years; a range from 4 to 73) diagnosed with soft tissue tumor were evaluated by both conventional diagnostic imaging and FDG-PET. Valid reference test of the local lesion was the histopathologic diagnosis, which was measured in all patients. The suspecting metastasis in the imaging studies was validated by pathology or follow up imaging for at least 6 months. Each imaging diagnosis was made independently. The accuracy of each diagnostic method was evaluated. The incremental cost accuracy ratio was determined in each diagnostic method. Results: For detection of local lesion, sensitivity, specificity, and accuracy for MRI and FDGPET scans were 91%, 57%, 83% and 95%, 43%, 83% respectively. For detection of distant lesion, sensitivity, specificity, accuracy for conventional diagnostic methods and FDG-PET scans were 77%, 89%, 87% and 92%, 94%, 93% respectively. The incremental cost accuracy ratio (ICAR) of FDG-PET for detection of distant lesion was 145,000won/%. According to ICAR for each tumor grade, PET strategy is most cost-effective at high grade tumors. Conclusions: For detection of local lesion such as recurrence or remnant tumor, FDG-PET scan was not more accurate than MRI. However, It was more accurate for detection of metastatic lesion than conventional methods. For detection of high grade tumor, PET was most costeffective than for detection of lower grade tumor.

• Journal of Gastric Cancer
• /
• v.2 no.4
• /
• pp.195-199
• /
• 2002

Purpose: Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) is the most significant angiogenic factor and a selective mitogen for endothelial cells. VEGF, also known as the vascular permeability factor, acts on endothelial cells to increase microvascular permeability and directly stimulate the growth of new blood vessels. Several studies have reported that the expression of VEGF is correlated with hematogenous recurrence via angiogenesis in gastric carcinomas. This research evaluated the relationship between the expression of VEGF and hepatic and peritoneal recurrence in gastric carcinomas. Materials and Methods: Thirty specimens resected from patients with primary gastric carcinomas who had undergone curative resections were divided into three group: Group I, early gastric carcinomas without recurrence; Group II, advanced gastric carcinomas with hepatic recurrence; and Group III, advanced gastric carcinomas with peritoneal recurrence. The expression of VEGF and the density of the microvessel count were examined using immunohistochemistry. Results: 1) The expression of VEGF in Group II and Group III ($63.2\pm\24.3\%$) was stronger than that in Group I ($7\pm\4.2\%$). The expression of VEGF in Group II ($76.5\pm\13.2\%$) was stronger than that of the Group III ($50\pm\14.2\%$) (P<0.05). 2) The microvessel count in Group II ($49.9\pm14.5$) was more than that in Group I ($8.6\pm2.6$) and Group III ($29.1\pm18.1$) (P<0.05). 3) The microvessel count was increased significantly with increasing the expression of VEGF. Conclusions: The expression of VEGF is associated with advanced stomach cancer and hepatic recurrence has a higher expression of VEGF than peritoneal recurrence with neovascularization. Thus the expression of VEGF can be considered to be a useful indicator of recurrence in gastric carcinoma and especially in hepatic recurrence.

• Journal of Gastric Cancer
• /
• v.7 no.2
• /
• pp.102-106
• /
• 2007

Gastric carcinoid tumor is a neoplasm that arises from enterochromaffine-like (ECL) cells in the gastric fundus. It is a rare disease that comprises less than 2% of all gastric neoplasms; however its incidence has been recently increasing. We experienced one case of gastric carcinoid tumor that was revealed to be multiple polypoid lesions. A 29-year-old female patient visited a hospital three years ago due to syncope. The blood hemoglobin was measured as 6.0 g/dl. Gastroscopy revealed multiple polypoid lesions with bleeding; therefore endoscopic clipping was performed. The polyps were diagnosed as carcinoid tumor via endoscopic biopsy. She was transferred to our hospital because of persistent iron deficiency anemia that was caused by bleeding at the gastric polyps. Gastroscopy revealed more than twenty various-sized polypoid lesions from the mid-body to the antrum. The blood hemoglobin level was 9.0g/dl. Total gastrectomy was performed under the diagnosis of gastric carcinoid tumor with bleeding. All of the gastric polyps were diagnosed as carcinoid tumors, and any metastasis to the regional lymph nodes was not found. Eighteen months after operation, the blood hemoglobin was increased to 12.8g/dl with no evidence of recurrence. Surgical resection should be considered for treating gastric carcinoid tumor with continuous bleeding.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5907-5912
• /
• 2015

Purpose: To evaluate and update evidence for prognostic effects of kidney-sparing (KS) management and nephroureterectomy (NU) for upper tract urothelial carcinomas. Materials and Methods: Pubmed, Embase and the Cochrane Library were retrieved for the identification of comparative studies of kidney-sparing procedure and nephroureterectomy for upper tract urothelial carcinoma prior to December 2014. The data were extracted independently by 2 reviewers and the quality of the included studies was assessed. Review Manager 5.3 and STATA 13 were used to perform the meta-analysis. Results: Twenty-three observational studies including 1,587 KS and 3,996 NU were evaluated. The results of the meta-analysis showed that nephroureterectomy had no significant benefit with regard to intravesical recurrence (IRFS), metastasis (MFS), cancer specific survival (CSS) and overall survival (OS) except the total tumor recurrence (RFS) when compared with kidney sparing management. The respectively pooled outcomes were HR 1.36 (0.69-2.68, P=0.38) for IRFS, 1.09 (0.59-2.01, P=0.78) for MFS, 1.17 (0.77-1.79, P=0.47) for CSS, 1.50 (0.90-2.48, P=0.12) for OS and 1.61 (1.03-2.51, P=0.04) for RFS. Conclusions: On the whole, kidney-sparing management had equivalent prognostic effect on upper tract urothelial carcinoma as the standard nephroureterectomy except in tumor recurrence. However, the results should be interpreted with caution for lack of stage and grade stratification and multi-center randomized controlled trials are still needed to verify our results.