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Articles by J. H Kim
Total Records ( 24 ) for J. H Kim
  J. H Kim , K. H Chang , D.G Na , S. H Park , E Kim , D.H Han , H. M Kwon , C. H Sohn and Y.J. Yim
 

BACKGROUND AND PURPOSE: Meningeal inflammatory myofibroblastic tumor (IMT) has been rarely reported, and its prognosis is still unclear. Our purpose was to describe the imaging features of patients with meningeal IMT and their results on follow-up studies.

MATERIALS AND METHODS: Twenty-four MR images in 10 consecutive patients with pathologically proved meningeal IMTs were retrospectively evaluated, focusing on the lesion distribution, signal intensity (SI), and contrast-enhancement pattern with a review of the clinical records.

RESULTS: Eight patients with intracranial IMT showed localized (n = 4) or diffuse (n = 4) dural thickening, a single mass (n = 5) or 2 (n = 2) dural-based masses with surrounding edema, dural venous sinus thrombosis (n = 5), and leptomeningeal involvement (n = 5). Extracranial involvement of the mastoid (n = 2) and orbit (n = 2) was also associated. Each of the 2 patients with intraspinal IMT showed a dural-based mass and a segmental dural thickening, respectively. All of the thickened dura showed low SI on T2-weighted images, iso-SI on T1-weighted images, and diffuse contrast enhancement. Variable recurrences with dural-based masses, mastoid involvement, or nasolacrimal duct involvement were observed in all 4 patients with diffuse intracranial IMT, but not in the others.

CONCLUSIONS: Localized or diffuse dural thickening of T2 low SI and diffuse contrast enhancement combined with dural-based masses are a common MR imaging finding of meningeal intracranial IMT. Adjacent leptomeningeal involvement and dural venous sinus thrombosis are frequently associated. The diffuse type has a tendency toward recurrence.

  J. H Kim , J. H Shin , H. Y Song , J. Y Ohm , J. M Lee , D. H Lee and S. W. Kim
 

OBJECTIVE. The purpose of our study was to evaluate the clinical results of temporary stenting followed by radiation and/or chemotherapy in patients with inoperable malignant tracheobronchial strictures.

CONCLUSION. Temporary stenting combined with radiation therapy and/or chemotherapy may be clinically effective in the palliative treatment of patients with malignant tracheobronchial strictures. Stent placement may serve as an effective bridge to radiation and/or chemotherapy, allowing the latter to consolidate durable relief of obstructing symptoms by reducing tumor burden. Furthermore, our treatment strategy may increase patients' quality of life by reducing stent-related complications.

  J. H Kim , H. Y Song , J. H Shin , H. T Hu , S. K Lee , H. Y Jung and J. H. Yook
 

OBJECTIVE. The objective of our study was to compare the clinical effectiveness of metallic stent placement for relief of gastric outlet obstruction caused by gastric carcinoma and pancreatic carcinoma.

MATERIALS AND METHODS. A total of 207 patients with gastric outlet obstruction caused by inoperable gastric carcinoma (n = 147) or pancreatic carcinoma (n = 60) underwent metallic stent placement.

RESULTS. Technical success of metallic stent placement was achieved in all patients. Clinical success was achieved in 97% and 93% of patients with gastric and pancreatic carcinoma, respectively (p = 0.286). The overall complication rate did not differ significantly between the gastric (29%) and pancreatic (23%) carcinoma groups (p = 0.441). Stent collapse was significantly more frequent in the gastric carcinoma group (11%) than the pancreatic carcinoma group (2%) (p = 0.027), whereas serious complications, including gastrointestinal bleeding and intestinal perforation, occurred more frequently in the pancreatic (7%) than the gastric (1%) carcinoma group (p = 0.026). The cumulative survival period was significantly longer in the gastric carcinoma (median, 153 days) than the pancreatic carcinoma (median, 90 days) group (p = 0.041), but cumulative stent patency did not differ significantly between the gastric carcinoma (median, 350 days) and pancreatic carcinoma (median, 385 days) groups (p = 0.415).

CONCLUSION. Metallic stent placement was clinically effective in the palliative treatment of gastric outlet obstruction in patients with gastric and pancreatic carcinoma. The two groups differed significantly in the rates of stent collapse and serious complications and patient survival after stent placement.

  J. H Kim , H. Y Song , Y. D Li , J. H Shin , J. H Park , C. S Yu and J. C. Kim
 

OBJECTIVE. The purpose of this study was to compare, focusing on colonic perforation and stent migration, the clinical safety and efficacy of dual-design expandable colorectal stents with flared ends with those of stents with bent ends in the treatment of patients with malignant colorectal obstruction.

SUBJECTS AND METHODS. A total of 122 patients with malignant colorectal obstruction underwent implantation of dual-design stents with flared (n = 69) or bent (n = 53) ends.

RESULTS. Stent placement was technically successful in 116 of 122 patients (95.1%), 65 of 69 patients (94.2%) with flared-end stents and 51 of 53 patients (96.2%) with bent-end stents (p > 0.05). Clinical success was achieved within 2 days in 61 of 65 patients (93.8%) with bent-end stents and in 46 of 51 patients (90.2%) with flared-end stents (p > 0.05). Complications included seven cases of colonic perforation (6%), seven cases of stent migration (6%), three cases of tumor overgrowth (2.6%), four cases of severe rectal pain (3.4%), and four cases of bleeding (3.4%). There were no significant differences between the rates of colonic perforation and stent migration in the two groups (6.2% vs 5.9%), and the overall complication rates were similar (p > 0.05).

CONCLUSION. Dual-design expandable colorectal stents with flared ends and those with bent ends are equally safe and effective, having similar perforation and migration rates.

  S. Y Ryu , S. I Park , B. H Nam , I Kim , C. W Yoo , J. H Nam , K. H Lee , C. H Cho , J. H Kim , S. Y Park , B. G Kim and S. B. Kang
 

Background: This study was to investigate the prognostic significance of clinicopathologic characteristics in patients with clear-cell carcinoma (CCC) of the ovary.

Materials and methods: Two hundred and one patients with CCC of the ovary were registered in the Korean Gynecologic Oncology Group. The Korean Gynecologic Pathology Study Group reviewed the pathological slides centrally, using a universal grading system. The prognostic significances of clinicopathologic factors were evaluated by multivariate analysis.

Results: Most of the patients were diagnosed at an early stage (stage I, 61.3%), and the overall 5-year survival rate was 57%. Early-stage disease showed a favorable prognosis, but advanced diseases showed poor prognosis. Stage of disease was the only significant prognostic factor on multivariate analysis (P < 0.001). However, universal grade and residual tumor also showed prognostic significance on the forward stepwise likelihood ratio test. There was no survival difference observed between patients treated with paclitaxel-based and those treated with platinum-based combination chemotherapy.

Conclusions: The stage, residual tumor, and universal grade were significant prognostic factors in patients with CCC of the ovary. The universal grading system is applicable in determining prognosis of CCC of the ovary. Further clinical trials for optimal chemotherapy are in need.

  L Yang , J. H Kim , K. D Kovacs , J. G Arroyo and D. F. Chen
 

Objective  To determine whether systemic minocycline can protect photoreceptors in experimental retinal detachment (RD).

Methods  Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling.

Results  Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD.

Conclusions  Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD.

Clinical Relevance  Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.

  Y. J Jang , M. S Park , S. S Park , J. H Kim , H An , S. H Park , S. J Kim , C. S Kim and Y. J. Mok
 

Background  The results of gastric cancer treatment have improved during the past 2 decades. In addition to early diagnosis, surgeon experience and subspecialty may influence long-term outcomes. This study analyzed data accumulated during the past 20 years regarding the impact of surgical subspecialty on gastric cancer prognosis.

Design  A 20-year, retrospective study.

Setting  Korea University Guro Hospital, Seoul.

Patients  A total of 2797 patients admitted between 1984 and 2003 with surgically treated, pathologically confirmed, primary gastric adenocarcinoma.

Main Outcome Measure  Long-term survival.

Results  The incidence of total gastrectomy and the number of retrieved lymph nodes increased during the study period. In curative cases, 5-year survival improved from 66.1% to 76.6%, and this survival gain was restricted to stages I, III, and IV. A Cox proportional hazards regression model showed that age, sex, tumor location, type of resection, stage, and the interaction between period of study and surgical subspecialty were independent prognostic factors.

Conclusions  This large, long-term cohort study demonstrates that the management of gastric cancer has been largely successful, with favorable trends in prognostic factors. Successful outcomes are realized more often by gastric surgical specialists. Efforts must be made to improve the treatment of patients with stage II gastric cancer because the improvements in long-term results have plateaued.

  J. H Kim , W. C Kim , M. S Waterman , S Park and L. M. Li
 

Summary: Haplotype assembly is becoming a very important tool in genome sequencing of human and other organisms. Although haplotypes were previously inferred from genome assemblies, there has never been a comparative haplotype browser that depicts a global picture of whole-genome alignments among haplotypes of different organisms. We introduce a whole-genome HAPLotype brOWSER (HAPLOWSER), providing evolutionary perspectives from multiple aligned haplotypes and functional annotations. Haplowser enables the comparison of haplotypes from metagenomes, and associates conserved regions or the bases at the conserved regions with functional annotations and custom tracks. The associations are quantified for further analysis and presented as pie charts. Functional annotations and custom tracks that are projected onto haplotypes are saved as multiple files in FASTA format. Haplowser provides a user-friendly interface, and can display alignments of haplotypes with functional annotations at any resolution.

  A. Y Oh , J. H Kim , J. W Hwang , S. H Do and Y. T. Jeon
  Background

In this prospective, randomized, double-blind study, we evaluated and compared the incidence of postoperative nausea and vomiting (PONV) after paediatric strabismus surgery with two different anaesthetic methods, sevoflurane or remifentanil–sevoflurane.

Methods

In total, 78 paediatric patients (aged 6–11 yr) undergoing strabismus surgery were enrolled and randomly assigned to two groups, sevoflurane (Group S) and remifentanil–sevoflurane (Group R). Anaesthesia was maintained with 2–3% sevoflurane in Group S (n=39) or with a continuous infusion of remifentanil combined with 1% sevoflurane in Group R (n=39), both using 50% N2O/O2. Arterial pressure and heart rate before induction, after tracheal intubation, after skin incision, and at the end of surgery were recorded. The incidence of PONV in the post-anaesthesia care unit, the day surgery care unit, and at home 24 h after surgery was recorded.

Results

Arterial pressure and heart rate were stable throughout the surgery, but were significantly lower in Group R than in Group S after tracheal intubation and skin incision. The incidence of PONV and postoperative vomiting was 17.9%/17.9% and 12.8%/10.2% (Group S/Group R) at the respective time points; values were comparable between the groups.

Conclusions

The incidence of PONV after paediatric strabismus surgery under sevoflurane anaesthesia was relatively low, and combining remifentanil with sevoflurane did not further increase the incidence.

  Y. J Kim , J. S Lee , K. S Hong , J. W Chung , J. H Kim and K. B. Hahm
 

Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammation-dysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid–reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of β-catenin–accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression. Cancer Prev Res; 3(8); 963–74. ©2010 AACR.

  Y. J Kim , K. S Hong , J. W Chung , J. H Kim and K. B. Hahm
 

The emergence of infliximab was an epochal event in the treatment of inflammatory bowel disease (IBD). Because colitis-associated cancers arose in the setting of chronic inflammation, during which "inflammation-dysplasia-carcinoma sequence" prevails and anti-inflammatory agents can prevent carcinogenesis, we hypothesized whether infliximab can prevent colitic cancer in animal models for which C57BL/6 mice were exposed to 15 cycles of dextran sulfate sodium (DSS), with each cycle consisting of 0.7% DSS for 1 week followed by sterilized water for 10 days. Infliximab (4 mg/kg i.v.) was given on the 1st, 3rd, and 7th weeks or 25th, 27th, and 31st weeks of cycle according to "step-up" versus "top-down" strategy. Molecular change about inflammation and carcinogenesis was compared between groups. Multiple colorectal tumors developed in 75% to 80% of control mice, whereas only 16.7% of mice treated with infliximab on the 1st, 3rd, and 7th weeks developed colon tumors. Significant decreases in tumor necrosis factor- level, mast cell number, and the expression of inflammatory cytokines were observed in top-down strategy using infliximab. The expression and activity of matrix metalloproteinase-9 (MMP-9) and MMP-11 were significantly decreased in mice treated with infliximab accompanied with attenuated numbers of "β-catenin–accumulated crypts." In animal group where infliximab was administered at later stage of 25th, 27th, and 31st weeks, no reduction in tumorigenesis was noted. These biological effects of infliximab were further explored in in vitro experiment using Raw264.7 and Jurkat T cells. Conclusively, earlier and intensive therapy with infliximab should be considered for either mitigating clinical course or preventing ultimate development of colitic cancer in high-risk IBD patients. Cancer Prev Res; 3(10); 1314–33. ©2010 AACR.

  T Truong , W Sauter , J. D McKay , H. D Hosgood , C Gallagher , C. I Amos , M Spitz , J Muscat , P Lazarus , T Illig , H. E Wichmann , H Bickeboller , A Risch , H Dienemann , Z. F Zhang , B. P Naeim , P Yang , S Zienolddiny , A Haugen , L Le Marchand , Y. C Hong , J. H Kim , E. J Duell , A. S Andrew , C Kiyohara , H Shen , K Matsuo , T Suzuki , A Seow , D. P. K Ng , Q Lan , D Zaridze , N Szeszenia Dabrowska , J Lissowska , P Rudnai , E Fabianova , V Constantinescu , V Bencko , L Foretova , V Janout , N. E Caporaso , D Albanes , M Thun , M. T Landi , J Trubicka , M Lener , J Lubinski , Wang EPIC lung , A Chabrier , P Boffetta , P Brennan and R. J. Hung
 

Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 x 10–4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89–0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85–0.95), P = 1 x 10–4]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations.

  L Santhanam , E. C Tuday , A. K Webb , P Dowzicky , J. H Kim , Y. J Oh , G Sikka , M Kuo , M. K Halushka , A. M Macgregor , J Dunn , S Gutbrod , D Yin , A Shoukas , D Nyhan , N. A Flavahan , A. M Belkin and D. E. Berkowitz
 

Rationale: Although an age-related decrease in NO bioavailability contributes to vascular stiffness, the underlying molecular mechanisms remain incompletely understood. We hypothesize that NO constrains the activity of the matrix crosslinking enzyme tissue transglutaminase (TG2) via S-nitrosylation in young vessels, a process that is reversed in aging.

Objective: We sought to determine whether endothelium-dependent NO regulates TG2 activity by S-nitrosylation and whether this contributes to age-related vascular stiffness.

Methods and Results: We first demonstrate that NO suppresses activity and increases S-nitrosylation of TG2 in cellular models. Next, we show that nitric oxide synthase (NOS) inhibition leads to increased surface and extracellular matrix–associated TG2. We then demonstrate that endothelium-derived bioactive NO primarily mediates its effects through TG2, using TG2–/– mice chronically treated with the NOS inhibitor l-NG-nitroarginine methyl ester (L-NAME). We confirm that TG2 activity is modulated by endothelium-derived bioactive NO in young rat aorta. In aging rat aorta, although TG2 expression remains unaltered, its activity increases and S-nitrosylation decreases. Furthermore, TG2 inhibition decreases vascular stiffness in aging rats. Finally, TG2 activity and matrix crosslinks are augmented with age in human aorta, whereas abundance remains unchanged.

Conclusions: Decreased S-nitrosylation of TG2 and increased TG activity lead to enhanced matrix crosslinking and contribute to vascular stiffening in aging. TG2 appears to be the member of the transglutaminase family primarily contributing to this phenotype. Inhibition of TG2 could thus represent a therapeutic target for age-associated vascular stiffness and isolated systolic hypertension.

  H. E Park , S. A Chang , H. K Kim , D. H Shin , J. H Kim , M. K Seo , Y. J Kim , G. Y Cho , D. W Sohn , B. H Oh and Y. B. Park
 

Background— The effects of left ventricular (LV) loading conditions on LV dyssynchrony have not been elucidated. We modified LV loading conditions to reveal their effects on echocardiography-derived LV dyssynchrony index (LVdys) in patients with documented nonischemic dilated cardiomyopathy.

Methods and Results— Thirty-seven patients were consecutively enrolled. After baseline measurements, pneumatic compression of the lower extremities (Pcom) was used to increase LV afterload. Subsequently, sublingual nitroglycerin (SL-NG) was administered to modify preload. Conventional echocardiographic parameters, LVdys (by speckle-tracking radial strain analysis) and LV end-systolic wall stress (LV-ESWS), were calculated under each condition. LVdys-6 (defined as the maximal difference in time-to-peak radial strain between 6 myocardial segments) and LV-ESWS increased under Pcom (for LVdys-6, 159±117 at baseline versus 239±140 ms under Pcom, P<0.05; for LV-ESWS, 191±63 versus 228±80 g/m2, P<0.05) After SL-NG application, both parameters decreased significantly (for LVdys-6, 239±140 under Pcom versus 147±103 ms after SL-NG, P<0.05; for LV-ESWS, 228±80 under Pcom versus 189±67 g/m2 after SL-NG, P<0.05). When the presence of LV dyssynchrony was defined as the absolute difference in time-to-peak radial strain between the anteroseptal and posterior segments (LVdys-2), the results were unchanged. Using 130 ms as a cutoff value, the proportion of patients with LV dyssynchrony changed significantly (29.7% at baseline, 45.9% under Pcom, and 35.1% after SL-NG). When the presence of LV dyssynchrony was defined as standard deviation of the time to peak radial strain for 6 segments (LVdys-SD), the results were same. LVdys and LV-ESWS showed a modest but significant association with each other (r=0.47, P<0.001 for LVdys-6; r=0.41, P<0.001 for LVdys-2; r=0.46, P<0.001 for LVdys-SD).

Conclusions— To the best of our knowledge, the present study provides the first evidence of a significant association between LVdys and LV loading status, reflective of a dynamic nature of LVdys. Accordingly, LV loading conditions should be taken into account when echocardiographic LVdys is used for clinical decision-making of selecting candidates for cardiac resynchronization therapy or when it is used as a surrogate marker of prognosis.

  J. H Kim and J. L. Workman
 

Histone acetylation is generally considered a mark involved in activating gene expression by making chromatin structures less compact. In the April 1, 2010, issue of Genes & Development, Xhemalce and Kouzarides (pp. 647–652) demonstrate that the acetylation of histone H3 at Lys 4 (H3K4) plays a role in the formation of repressive heterochromatin in Schizosaccharomyces pombe. H3K4 acetylation mediates a switch of chromodomain proteins associated with methylated H3K9 during heterochromatin assembly.

  K. C Chun , D. Y Kim , J. H Kim , Y. M Kim , Y. T Kim and J. H. Nam
 

To date, only seven women with Stage Ib1 to IIb cervical cancer during pregnancy treated with neoadjuvant chemotherapy followed by radical surgery have been reported. We describe three cases of pregnant women with Stage Ib1 to IIa cervical cancer who were treated with paclitaxel plus platinum neoadjuvant chemotherapy followed by radical surgery. The first patient had a Stage Ib1 small cell neuroendocrine carcinoma of the cervix, the second had a Stage IIa, 8 cm squamous cell carcinoma of the cervix and the third had a Stage Ib2 squamous cell carcinoma and positive lymph nodes. The three patients and their newborns were followed up. All patients had a partial or complete response to neoadjuvant chemotherapy. Two of these patients developed recurrences and one died due to progressive disease at 49 months. All neonates were healthy and had no abnormalities. In conclusion, neoadjuvant chemotherapy with paclitaxel and platinum followed by radical surgery may be an option for pregnant women with invasive cervical cancer.

  M. N Lee , S. N Lee , S. H Kim , B Kim , B. K Jung , J. H Seo , J. H Park , J. H Choi , S. H Yim , M. R Lee , J. G Park , J. Y Yoo , J. H Kim , S. T Lee , H. M Kim , S Ryeom , K. W Kim and G. T. Oh
  Background

Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A225) acetylates HIF-1, triggering its degradation, and thus may play a role in decreased expression of VEGFA.

Methods

We generated ApcMin/+/mARD1A225 transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A225 were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A225 acetylation of Lys532 in HIF-1, we injected B16F10-mARD1A225 cell lines stably expressing mutant HIF-1/K532R into mice and measured metastasis. All statistical tests were two-sided, and P values less than .05 were considered statistically significant.

Results

ApcMin/+/mARD1A225 transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than ApcMin/+ mice (n = 21) (number of intestinal polyps per mouse: ApcMin/+ mice vs ApcMin/+/mARD1A225 transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; P < .001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A225-overexpressing cells than in mice injected with control cells (P < .01). Moreover, overexpression of mARD1A225 decreased VEGFA expression and microvessel density in tumor xenografts (P < .04) and ApcMin/+ intestinal polyps (P = .001). Mutation of lysine 532 of HIF-1 in B16F10-mARD1A225 cells prevented HIF-1 degradation and inhibited the antimetastatic effect of mARD1A225 (P < .001).

Conclusion

mARD1A225 may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis.

  T Truong , R. J Hung , C. I Amos , X Wu , H Bickeboller , A Rosenberger , W Sauter , T Illig , H. E Wichmann , A Risch , H Dienemann , R Kaaks , P Yang , R Jiang , J. K Wiencke , M Wrensch , H Hansen , K. T Kelsey , K Matsuo , K Tajima , A. G Schwartz , A Wenzlaff , A Seow , C Ying , A Staratschek Jox , P Nurnberg , E Stoelben , J Wolf , P Lazarus , J. E Muscat , C. J Gallagher , S Zienolddiny , A Haugen , H. F. M van der Heijden , L. A Kiemeney , D Isla , J. I Mayordomo , T Rafnar , K Stefansson , Z. F Zhang , S. C Chang , J. H Kim , Y. C Hong , E. J Duell , A. S Andrew , F Lejbkowicz , G Rennert , H Muller , H Brenner , L Le Marchand , S Benhamou , C Bouchardy , M. D Teare , X Xue , J McLaughlin , G Liu , J. D McKay , P Brennan and M. R. Spitz
  Background

Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies.

Methods

Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case–control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided.

Results

Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 x 10–26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 x 10–10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 x 10–8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 x 10–5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer.

Conclusions

In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

  K. E Lee , J. H Kim , M. K Jung , T Arii , J. S Ryu and S. S. Han
 

The flagellated protozoan Trichomonas vaginalis has been widely studied owing to its medical significance and unique structure. The complicated three-dimensional (3D) structure of the cellular components of T. vaginalis was reconstructed from serial sections to enable observation of the spatial features of the whole cell. Electron tomography was used to examine the detailed structure of the cellular organelles. Tomographic reconstruction showed the mastigont system and the parabasal filament of T. vaginalis in detail. The last thin filament (Pf3) was located close to the adjacent filament, and the two filaments appeared to be vertically parallel in the cross-sectional view. It is likely that Pf3 cannot be distinguished from the adjacent filament in 2D images obtained from transmission electron microscopy. Our 3D reconstruction of T. vaginalis revealed the presence of an additional striated fiber, and 3D reconstruction by electron tomography showed twisting of the split parabasal filament.

  M Park , E Shin , M Won , J. H Kim , H Go , H. L Kim , J. J Ko , K Lee and J. Bae
 

Mutations in FOXL2 are responsible for blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type I, in which affected women exhibit premature ovarian failure. FOXL2-null mice showed defects in granulosa cell development during folliculogenesis. We screened a rat ovarian yeast two-hybrid cDNA library to identify FOXL2-interacting proteins and found steroidogenic factor-1 (SF-1). Here, we show that human FOXL2 and SF-1 proteins interact in human granulosa cells and that FOXL2 negatively regulates the transcriptional activation of a steroidogenic enzyme, CYP17, by SF-1. Furthermore, FOXL2 mutants found in blepharophimosis-ptosis-epicanthus inversus syndrome type I patients lost the ability to repress CYP17 induction mediated by SF-1. Chromatin immunoprecipitation and EMSA results further revealed that FOXL2 inhibited the binding of SF-1 to the CYP17 promoter, whereas the FOXL2 mutants failed to block this interaction. Therefore, this study identifies a novel regulatory role for FOXL2 on a key steroidogenic enzyme and provides a possible mechanism by which mutations in FOXL2 disrupt normal ovarian follicle development.

  S. B Jang , C Ma , J. Y Lee , J. H Kim , S. J Park , A. R Kwon and B. J. Lee
 

The HP0827 protein is an 82-residue protein identified as a putative ss-DNA-binding protein 12RNP2 Precursor from Helicobacter pylori. Here, we have determined 3D structure of HP0827 using Nuclear Magnetic Resonance. It has a ferredoxin-like fold, β1–1–β2–β3–2–β4 (; -helix and β; β-sheet) and ribonucleoprotein (RNP) motifs which are thought to be important in RNA binding. By using structural homologues search and analyzing electrostatic potential of surface, we could compared HP0827 with other RNA-binding proteins (sex-lethal, T-cell restricted intracellular antigen-1, U1A) to predict RNA-binding sites of HP0827. We could predict that β sheets of HP0827, especially β1 and β3, are primary region for RNA binding. Consequently, similar to other RNA-binding proteins, RNP motifs (Y5, F45, F47), positively charged and hydrophobic regions (K32, R37, K40, K41, K43, R70, R73) are proposed as a putative RNA-binding sites. In addition, differences in amino acids composition of RNP motifs, N, C-terminal residues, loop-region fold and the orientation of 1-helix with other RNA recognition motif proteins could give specific biological functions to HP0827. Finally, the study on natural RNA target is also important to completely understand the biological function of HP0827.

 
 
 
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