Cytochrome P450 (CYP) enzymes are a large family of constitutive and inducible mono-oxygenase enzymes that play a central role in the oxidative metabolism of both xenobiotic and endogenous compounds. Several CYPs are involved in metabolism of oxysterols, which are cholesterol oxidation products whose expression may be dysregulated in inflammation-related diseases including cancer. This study focused on CYP39A1, which can metabolize 24-hydroxycholesterol (24-OH) that plays important roles in the inflammatory response and oxidative stress. We aimed to investigate the expression status of CYP39A1 and its transcription factor (RUNX2) in relation to clinical significance in cholangiocarcinoma (CCAs) and to determine whether 24-OH could induce oxidative stress in CCA cell lines. Immunohistochemistry showed that 70% and 30% of CCA patients had low and high expression of CYP39A1, respectively. Low expression of CYP39A1 demonstrated a significant correlation with metastasis. Our results also revealed that the expression of RUNX2 had a positive correlation with CYP39A1. Low expression of both CYP39A1 (70%) and RUNX2 (37%) was significantly related with poor prognosis of CCA patients. Interestingly, oxidized alpha-1 antitrypsin (ox-A1AT), an oxidative stress marker, was significantly increased in CCA tissues in which CYP39A1 and RUNX2 were down regulated. Additionally, immunocytochemistry showed that 24-OH could induce ox-A1AT in CCA cell lines. In conclusion, our study revealed putative roles of the CYP39A1 enzyme in prognostic determination of CCAs.
This study was designed to elucidate high-$K^+$ induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high $K^+$ (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high $K^+$ (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high $K^+$-induced relaxation. $K^+$ channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium ($Ba^{2+}$) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent $K^+$ channel (KV) blocker, inhibited high $K^+$ -induced relaxation, hence reversing to tonic contraction. High $K^+$-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and KV channel blocker sensitive high $K^+$-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high $K^+$-induced relaxation which was activated by NO/sGC pathway and by $K_V$ channel dependent mechanism.
Purpose: Although the role of squamous cell carcinoma antigen (SCC-Ag) as a predictive and prognostic factor for uterine cervical cancer has been identified in previous studies, 1) the effective patient group of screening for recurrence with SCC-Ag, 2) the relationship between SCC-Ag and recurrence site, and 3) the relationship between the change of SCC-Ag and treatment outcome or recurrence have not been described. Materials and Methods: The study included 506 patients with histologically proven uterine cervical cancer between January 1994 and December 2010. We determining the serum SCC-Ag level before treatment and after treatment, and conducted a retrospective review of the patients' records. We evaluated the sensitivity and specificity of SCC-Ag for the detection of tumor recurrence by comparing biochemical recurrence with clinical recurrence. Results: The pretreatment SCC-Ag level and the proportion of patients over 1.5 ng/mL were higher in poor prognostic patient group. In the univariate and multivariate analysis, pretreatment SCC-Ag showed a statistically significant correlation with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology. In patients with biochemical recurrence vs. those without, 5-year DFS and OS were 27.6 vs. 92.7% (p ${\leq}$ 0.001) and 53.7 vs. 92.5% (p ${\leq}$ 0.001), respectively. Conclusion: Our study reconfirmed the known function of pretreatment SCC-Ag, but could not confirm the function of biochemical response as a predictive factor for treatment and as a prognostic factor. There was no statistically significant relationship between SCC-Ag level and recurrence site. We confirmed the role of SCC-Ag as a follow-up tool for recurrence of disease and which patient groups SCC-Ag was more useful for.
Hwang, Ki Eun;Park, Chul;Seol, Chang Hwan;Hwang, Yu Ri;Hwang, June Seong;Jung, Jae Wan;Choi, Keum Ha;Jeong, Eun Taik;Kim, Hak Ryul
Tuberculosis and Respiratory Diseases
/
v.75
no.2
/
pp.59-66
/
2013
Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.
Kim, Young-Kyun;Kim, Su-Gwan;Lee, Jun-Gil;Lee, Mi-Hyang;Cho, Jae-O
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.27
no.1
/
pp.15-24
/
2001
The purpose of this study is to evaluate the tissue response in applying of various bone substitutes included toothash-plaster mixture, resorbable hydroxylapatite (HA) and demineralized freeze-dried bone and to show the clinical usefulness of toothash-plaster mixture for the repair of craniomaxillofacial bone defect. For this experiment, 100 Sprague-Dawley rats weighing 200gm or more were used. There were four experimental groups: group I, toothash-plaster mixture; group II, demineralized freeze-dried bone; group III, resorbable HA; and group IV, control group. A full thickness, round bone defect measuring 10mm in diameter was created in the midcranium, and the substitutes cited above were embedded in the experimental rats based on their group assignment. Blood clot was filled in the rats assigned to the control group. Experimental rats were sacrificed on the 1st, 3rd, 5th, 8th, 12th and 24th week after implantation and stained with the hematoxylineosin, Masson's Trichrome, using Van Gieson's stain method, and were examined under light microscope. The results were as follows: 1. In all the groups, prominent inflammatory reaction and the infiltration of multinucleated giant cells were noted during the early stage. Gradual healing decreased this reaction. 2. Among the rats in the experimental group II, which were given demineralized freeze-dried bone implants, active formation of new bone traveculae manifested. Chondroid tissues appeared, and it was suggested that the defect was filled with newly formed bone by virtue of osteoinductive activity. On the 12th week after the experiments, most of the defect was filled with newly formed bone trabeculae. 3. In experimental groups I and III, it was noted that HA manifested a healing process similar to that characterized by the toothash-plaster mixture, but inflammatory reaction was more prominent in experimental group I. Active osteoblasts were observed along the periphery of osteoid tissues, while newly formed bone trabeculae appeared adjacent to the implanted materials three weeks later. Formation increased to the extent that newly formed bone trabeculae fused directly with the host bone. Increase in new bone ingrowth into the filling materials was revealed by both experimental groups. 4. In the control group, new bone formation adjacent to the host bone was observed, but most of the defect was filled with mature connective tissue 24 weeks after the experiments.
To clarify the clinicopathologic features of small-cell carcinomas (SCC) of the stomach, we reviewed three cases of surgically treated SCC. The first case was a pure SCC, with severe pancreatic invasion and peritoneal seeding. A gastro-jejunostomy was performed. Postoperative chemotherapy was performed with CDDP and VP-16 (8 cycles) but showed disease progression (PD); a consecutive chemotherapy with CDDP and irinotencan (2 cycles) also showed PD. A third line with CDDP, VP16, ifosfamide, and mesna was followed by a 4th line (CDDP and Taxol). The male patient died with liver metastasis and peritoneal seeding 14 months after the operation. The second case was a SCC mixed with a poorly differentiated adenocarcinoma. Profound lymphadenopathy and liver metastasis were found. Two cycles of preoperative chemotherapy with TS-1 and CDDP were performed, which showed nearly complete remission for lymphadenopathy and partial response for the primary tumor site and liver metastatic lesion. A total gastrectomy and extended lymphadenectomy was performed. There were no viable cancer cells in 35 retrieved lymph nodes. Postoperative chemotherapy using the same regimen was performed for 4 cycles. Enlarged liver metastasis was found at the follow-up CT scan, so a posterior segmentectomy of liver was performed. After liver surgery, the chemotherapy regimen was changed to irinotecan and cisplatin. This male patient has been in good health for the f4 months since gastric surgery. The third case was a pure SCC, and a subtotal gastrectomy was performed curatively. That male patient received 5 cycles of TS-1 and is still in good health 14 months after operation.
Pulmonary hemangiomatosis is a rare disease of unknown etiology characterized by diffuse proliferating microvessels that infiltrate not only the lung but also all of the thoracic tissues. The disease is rapidly progressive and usually results in death due to complications of pulmonary hypertension and pulmonary hemorrhage. There are two histologic patterns of pulmonary hemangiomatosis : capillary and cavernous. We describe a 21-year-old man with cavernous-type pulmonary hemangiomatosis presented with right side shoulder pain. He was treated with percutaneous transarterial embolization and then followed with interferon alfa-2a for one year with favorable clinical and radiological response.
The pro-inflammatory cytokine tumor necrosis factor-$\alpha$ (TNF-$\alpha$) is an important mediator of the immune response in hepatitis B virus (HBV) infection. Since the production of TNF-$\alpha$ is mostly regulated at the transcriptional level and polymorphisms in the TNF-$\alpha$ promoter alter its expression, TNF-$\alpha$ promoter polymorphisms could affect the pathogenesis of chronic HBV infection. In this study, we investigated the potential association of TNF-$\alpha$ promoter polymorphisms with chronic HBV infection. The study included 181 patients with chronic HBV infection, 201 persons who had been spontaneously recovered from hepatitis B, and 170 unrelated healthy controls. The -308G/A and -238G/A polymorphisms in the TNF-$\alpha$ promoter were analyzed by PCR-restriction fragment length polymorphism. The distribution of both the -308 and -238 genotypes in the patient group was not statistically different from that in the spontaneous recovery and control groups (p>0.05). There was also no significant difference in the allele frequency between the groups (p>0.05). The results suggest that the TNF-$\alpha$ -308 and -238 promoter polymorphisms are not associated with the development of chronic HBV infection in the Korean population.
Jo, Su-Jung;Jang, Kyoung-Soo;Choi, Yong-Ho;Kim, Jin-Cheol;Choi, Gyung-Ja
Research in Plant Disease
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v.17
no.2
/
pp.161-168
/
2011
To establish simple and reliable screening method for resistant radish to Plasmodiophora brassicae Woron. using soil-drenching inoculation, the development of clubroot on radish seedlings inoculated with P. brassicae GN-1 isolate according to several conditions such as inoculum concentration, plant growth stage and incubation period after inoculation was studied. To select resistant radish against clubroot, 10-day-old seedlings were inoculated with P. brassicae by drenching the roots with the spore suspension of the pathogen to give $1{\times}10^9$ spores/pot. The inoculated seedlings were incubated in a growth chamber at $20^{\circ}C$ for 3 days then cultivated in a greenhouse ($20{\pm}5^{\circ}C$) for 6 weeks. Under the optimum conditions, 46 commercial cultivars of radish were tested for resistance to YC-1 (infecting 15 clubroot-resistant cultivars of Chinese cabbage) and GN-1 (wild type) isolates of P. brassicae. Among them, thirty-five cultivars showed resistance to both isolates and one cultivar represented susceptible response to the pathogens. On the other hand, the other cultivars showed different responses against the tested P. brassicae pathogens. The results suggest that this method is an efficient system for screening radish with resistance to clubroot.
Light and transmission electron microscopy of Batillus cornutus hemocytes revealed differences that the morphological distinctions between blast-like cell, granulocytes and hyalinocytes. Base on the morphological characteristics of the cells, we identified the eight types of hemocytes and present a categorization of the hyalinocytes into six sub-categories. The hemocytes of B. cornutus were observed basophilic cell under the light microscopy. Blast-like cells had a spherical profile with a central nucleus filling almost the whole cell. Granulocytes were characterized by presenting variable numbers of granules. This cell had spherical shape with diameter 7 ${\mu}m$ and smooth endoplasmic reticula, granules, mitochondria, glycogen granules in the cytoplasm. Hyalinocytes were the most abundant cell type. Especially, hyalinocyte VI had iirregular an amoebal shape and observed autophagosome and heterophagosome in the cytoplasm. From these results, it is concluded that there are eight types of cells in the hemolymph of B. cornutus. Further studies are now needed to identify the role of these hemocytes in the enzymological and immunological response.
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