• Oncology Letters
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• v.18 no.6
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• pp.5731-5738
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• 2019

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Novel biomarkers of ccRCC may provide crucial information on tumor features and prognosis. The present study aimed to determine whether the expression of γ-aminobutyric acid (GABA) A receptor subunit θ (GABRQ) could serve as a novel prognostic marker of ccRCC. GABA is the main inhibitory neurotransmitter in the brain that activates the receptor GABAA, which is comprised of three subunit isoforms: GABRA3, GABRB3 and GABRQ. A recent study reported that GABRQ is involved in the initiation and progression of hepatocellular carcinoma; however, the role of GABRQ in ccRCC remains unknown. In the present study, clinical and transcriptomic data were obtained from cohorts of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential GABRQ expression levels among early (TI and II), late (TIII and IV), nonmetastatic (M0) and metastatic (M1, primary tumor) stages of ccRCC samples were then identified. Furthermore, the use of GABRQ as a prognostic gene was analyzed using Uno's C-index based on the time-dependent area under the curve (AUC), the AUC of the receiver operating characteristic curve at 5 years, the Kaplan-Meier survival curve and multivariate analysis. The survival curve analysis revealed that low GABRQ mRNA expression was significantly associated with a poor prognosis of ccRCC (P<0.001 and P=0.0012 for TCGA and ICGC data, respectively). In addition, analyses of the C-index and AUC values further supported this discriminatory power. Furthermore, the prognostic value of GABRQ mRNA expression was confirmed by multivariate Cox regression analysis. Taken together, these results suggested that GABRQ mRNA expression may be considered as a novel prognostic biomarker of ccRCC.

• The Journal of the Korean bone and joint tumor society
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• v.10 no.2
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• pp.61-70
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• 2004

Purpose: We studied to decide the operative indication of the metastatic tumor in pelvis according to the oncologic results, the Eastern Cooperative Oncologic Group (ECOG) performance status and complication. Materials and methods: From May 1994 to May 2003, 9 patients who were performed on palliative treatment and 10 paitents on operative treatment due to metastatic tumor of pelvic bone were investigated. On palliative/operative group, the mean age of patients was 57.6/48.0 years old and the ratio of male to female was 5:4/7:3. Primary origins were 3 cases from kidney, 3 from cervix and 2 of lung, 2 of myeloma, 2 of Non-Hodgkin's Lymphoma, and 1 from breast, bladder, testis, prostate, stomach, liver and retroperitoneal leimyosarcoma respectively. The palliative treatment was performed in 5 cases with radiotherapy, 1 with chemotherapy, 2 with combined chemo-radiotherapy and 1 with percutaneous cementation. The operative methods were 1 case of bone cement insertion after curettage, 2 of Girdlestone with internal hemipelvectomy and 7 of reconstruction after wide excision. Reconstructions were done.: 1 case of bone cementation, 5 of autograft prosthesis composite with irradiation or pastuerization and 1 of saddle prosthesis. We have observed the oncologic results, the ECOG performance status and complication. Results: The oncologic results of palliative/operative groups are NED 0/1, AWD 2/6, DOC 1/2 and DOD 6/1. The ECOG performance status was changed from 1.5 into 4.3 in palliative group and from 2.6 into 2.2 in operative group. The complications were 3 cases of the prosthesis failure and 2 of infection. Conclusion: The indication of operation of metastatic pelvic tumor is decided in consideration of the patient's condition, the grade of malignancy in primary tumor and the life expectancy.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.99-116
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• 2016

We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.1-6
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• 2004

Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.

• Food Science and Biotechnology
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• v.17 no.5
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• pp.1106-1109
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• 2008

The anti-Helicobacter pylori activity, cytotoxicity, and anti-inflammatory activity of white ginseng extract (WGE) were investigated in vitro in this study. The antimicrobial effects of WGE toward H. pylori strains 52 J99, SSI, and 51 were tested using the disk diffusion method. Among these H. pylori strains, H. pylori 52 was the most sensitive, having the largest inhibition zone (19 mm), followed by J99, SSI, and 51. The zone of inhibition due to WGE increased significantly with increasing dosage. The cytotoxicity of WGE toward the human cancer cell lines A-549 (human lung carcinoma), HEC-1-B (human endometrial adenocarcinoma), HeLa (human uterin adenocarcinoma), and SW-156 (human kidney carcinoma) was measured using the 3-(4,5-dimethylthizol-2-yl)-2,5-diphenylate-tetrazolium bromide (MTT) assay. WGE exhibited an inhibitory effect on cell growth at 2.0 mg/mL for all tumor cell lines. An analysis of anti-inflammatory activity using the RAW 264.7 cell line showed that the inhibition of nitric oxide (NO) production increased as the WGE content increased. These results demonstrate the potential of WGE to be used as a health-promoting substance.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.409-412
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• 2013

Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.7-11
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• 1999

The present work was carried out to examine the effect of costunolide on the growth of several cells and characteristics of U-937 human leukemia-derived cell line. Costunolide produced a potent antitumor activity in vitro dependent on concentration against several tumor cells such as P-388, L-1210 leukemia and SNU-5 stomach cancer cells. However, it showed less cytotoxicity on normal cells such as Maccaccus rheus monkey kidney cells (MA-104) up to 200 ${\mu}M$ concentration. An effect of cell differentiation by costunolide was assessed by its ability to reduce nitroblue tetrazolium (NBT), and to induce phagocytosis of latex particles. In order to establish whether costunolide induces U-937 cells to differentiate toward macrophage or granulocyte, esterase activities was measured. Based on these results, we found that costunolide having cytotoxicity on U-937 human leukemia cells was explained through differentiation inducing activity.

• Journal of Veterinary Clinics
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• v.31 no.1
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• pp.73-76
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• 2014

A 10-year-old, female spayed mixed-breed dog with a history of vomiting and anorexia was examined. Abnormal findings of comlete blood count and serum chemistry included polycythemia, thrombocytopenia, hyper-globulinemia and hypoalbuminemia. Abdominal radiographs revealed severe unilateral renomegaly, and ultrasonography showed a left-sided renal mass. During the operation, left kidney was resected. Cytologial and histopathological examinations revealed neoplastic lymphoid proliferation with high mitotic figures in renal mass. Immunohistochemistry revealed tumor cells were CD3-positive and CD79${\alpha}$-negative, consistent with T-cell lineage. The renal mass of this case was diagnosed as renal T cell lymphosarcoma.

• Childhood Kidney Diseases
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• v.7 no.1
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• pp.103-105
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• 2003

Scrotal swelling may be acute or chronic, painful or painless. Common causes of scrotal swelling in newborns are hydrocele, inguinal hernia, testicular torsion, testicular tumor, scrotal hematoma, meconium peritonitis and epididymitis. Abrupt onset of a painful scrotal swelling necessitates prompt evaluation. Testicular torsion and incarcerated inguinal hernia require urgent surgical management. We report a case of scrotal swelling caused by a tunica vaginalis abscess in a 20-days-old boy. He was admitted to the hospital due to fever, irritability and left scrotal swelling with local heat, tenderness and redness. Exploratory laparotomy was performed to rule out testicular torsion. On the operative field, congestive erythematous inflammation on the left tunica vaginalis was noted and it was filled with a pus like discharge. The cultured organism was Streptococcus agalactiae(group B). He recovered quickly after debridement and administration of empirical antibiotics.