CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors

CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers.

Intraocular Lens Power Calculation for Cataract Surgery after LASIK in the Absence of Pre-LASIK Data

PURPOSE: To evaluate the correlation between the conventional method and the clinical history method those determine intraocular lens (IOL) power for cataract surgery in eyes with prior laser in situ keratomileusis (LASIK) in the absence of pre-LASIK data. METHODS: The medical records of 200 eyes in 100 patients who had been treated with LASIK for myopia and were followed up for more than 6 months were reviewed. The IOL powers by conventional method using post-LASIK keratometric value and by clinical history method were compared. RESULTS: The mean values of IOL powers by conventional method, and by clinical history method were +20.00+/-1.48D (+13.74~+23.23D) and +20.79+/-1.28D (+17.27~+24.32D), respectively. The following equation describes the regular relationship between the two METHODS: IOL(CHM) (clinical history method)=0.708*IOL(CM) (conventional method) +6.624 (r=0.816, p<.01). CONCLUSIONS: This equation may offer more accurate IOL power for cataract surgery in eyes with prior LASIK surgery in the absence of pre-LASIK data.

Comparison of Refraction-Derived Keratometric Value and Orbscan Corneal Power after Laser in Situ Keratomileusis

PURPOSE: To determine the Orbscan corneal power which gave the best correlation with refraction-derived keratometric value (clinical history method) after LASIK in cataract surgery. METHODS: A total of 38 consecutive eyes of 19 patients who were followed up for at least 1 year after LASIK were included in study. The refraction-derived keratometric values were correlated with Orbscan corneal power within 1, 2, 3, 4, and 5 mm diameter zones of keratometric, anterior and total selections of mean, axial, tangential and optical power maps. RESULTS: The Orbscan corneal power of the 5-mm zone optical power total map gave the best correlation with refraction-derived keratometric value. The following regular relationship in linear regression analysis was derived: RDKV(refraction-derived keratometric value)=0.9 X OPT5(corneal power of Orbscan optical power total map 5-mm zone)+4.941(r=0.883). CONCLUSIONS: These results indicate that the corneal power of the 5-mm zone optical power total map was the most appropriate to calculate IOL power in cataract surgery after LASIK when using Orbscan topography.

Intraocular Lens Power Calculation in the Absence of Pre-PRK Data in Moderate Myopic Eyes

PURPOSE: To evaluate the correlation between the conventional method and the clinical history method for intraocular lens power calculation for cataract surgery in eyes with previous photorefractive keratectomy in the absence of pre-PRK data. METHODS: The medical records of 38 eyes in 23 patients who had been treated with PRK for myopia and were followed up for more than 1 year were reviewed. The IOL powers by conventional method using post-PRK keratometric value and by clinical history method were compared. RESULTS: The mean values of IOL powers by conventional method, and by clinical history method were +20.58 +/- 1.10D (range, +16.37~+22.80D) and +21.06 +/- 0.85D (range, +18.85~+22.8D), respectively. The following equation describes the regular relationship between the two METHODS: IOLCHM (clinical history method)= 0.683*IOLCM (conventional method) +7.005 (r=0.878, p<.01). When the IOL powers by conventional method were applied to this equation, the mean difference of value between the IOL powers calculated from this equation and those of the clinical history method was?0.01 +/- 0.41D (range, -0.99~+0.76D). CONCLUSIONS: This equation will be helpful to calculate the IOL power for cataract surgery in eyes with previous PRK in the absence of pre-PRK data.

C-Terminal Serine Rich Region of IKK-beta Interacts with Bfl-1, a Homologue of Bcl-2 / 대한진단검사의학회지

BACKGROUND: Bcl-2 family proteins play a central role in regulating apoptosis. In human, over 20 members of this family have been identified to date. Bfl-1, a member of the Bcl-2 family, has been known to retard apoptosis in various cell lines. However, the function of Bfl-1 remains unclear. METHODS: In order to investigate the Bfl-1 function, we employed yeast two-hybrid system to identify the proteins which are capable of interacting with Bfl-1. The interaction of inhibitor kappaB kinase-beta (IKK-beta) and Bfl-1 was confirmed using glutathione S-transferase pull down assays. To determine which regions of IKK-beta were required for interaction with Bfl-1, we constructed 12 deletion mutants of IKK-beta and 5 deletion mutants of Bfl-1. RESULTS: Bfl-1 interacted with the C-terminal region of IKK-beta which is a subunit of IKK complex, and IKK-beta activity is very important in the NF-kappaB related pathway. In addition, the amino acids 673-745 of IKK-beta were important for Bfl-1 interactions, and amino acids 1-484 of Bfl-1, including Bcl-2 homology domains (BH1, BH2, BH3, BH4), were crucial for IKK-beta interactions. CONCLUSIONS: IKK beta C-terminus contains many serine residues as binding partner of Bfl-1. Our results suggested that Bfl-1 is involved in the NF-kappaB activation through interaction of IKK-beta and Bfl-1. Further studies need to be performed to understand functions of the IKK-beta and Bfl-1 associated with the regulation of the NF-kappaB activation pathway.

Neovascularization of the Optic Disc Associated with Acute Ophthalmic Artery Obstruction

PURPOSE: It has been reported that neovascularization of the optic disc (NVD) occurs in ocular ischemic syndrome, sickle cell hemoglobinopathy, ocular sarcoidosis, Eales' disease, and central retinal artery occlusion. However, NVD in acute ophthalmic artery occlusion had not been reported. Therefore, we report one unusual case of NVD in acute ophthalmic artery obstruction. METHODS: A 56 year-old man with complaint of abrupt decrease of visual acuity and periorbital discomfort underwent medical history taking, periorbital examination, fundus examination, and fluorescein angiography. He was followed up for 5 months RESULTS: Fundus examination showed segmentation of blood flow and diffuse retinal whitish opacity on the posterior pole around the center of the macula, without any cherry red spots in the perifoveal area. Fluorescein angiography showed a marked filling delay in the nasal retinal and choroidal circulations with a definite watershed zone involving the peripapillary choroid and macula. The retinal arteries filling and arteriovenous transit time were delayed. There was no light-perception vision and low intraocular pressure. Diabetes was found on systemic examination. Five weeks later, NVD and choroidal atrophy around the optic disc were detected. Panretinal photocoagulation was performed for the regression of NVD. NVD was regressed, but recurred.

Comparison of IOL Powers by Different Formulae Used in Corrected Method at Cataract Surgery in Eyes after PRK

PURPOSE: By statistical analysis, to evaluate the comparison of the intraocular lens (IOL) powers by different formulae in patients who have been treated with excimer laser photorefractive keratectomy (PRK) for mild to moderate myopia. METHODS: A total of 38 consecutive eyes of 23 patients who were treated with PRK for mild to moderate myopia have been followed up for more than 6 months. IOL powers by SRK-II, SRK/T, Binkhorst-II, HofferQ, Holladay formula using autorefractokeratometer measured keratometric (K) values by autorefractokeratometer (RK-2, Canon, Japan) and refraction derived K values were compared . RESULTS: The mean IOL powers using autorefractokeratometer measured K values and refraction derived K values were 20.46+/-0.92 and 20.57+/-0.86 diopter (D) by SRK-II, 20.69+/-0.93 and 20.81+/-0.88 D by SRK/T, 21.27+/-0.94 and 21.40+/-0.95 D by Binkhorst-II, 20.93+/-0.09 and 21.05+/-0.06 D by Hoffer Q, and 20.65+/-0.90 and 20.76+/-0.87 D by Holliday respectively. The mean IOL powers using autorefractokeratometer measured K values and refraction derived K values were high in oder of Binkhorst-II, HofferQ, SRK/T, Holladay, and SRK-II, but there was no significant statistical difference between the IOL powers by SRK/T and those by Holladay (p>0.05). In all formulae, the mean IOL powers using refraction derived K values were higher than the mean IOL powers using autorefractokeratometer measured K values, but there was no statistically significant difference (p>0.05). CONCLUSIONS: In patients with excimer laser PRK treatment for mild to moderate myopia, refractive error after cataract surgery is caused by IOL calculation formula as well as its method for IOL power. IOL powers by Binkhorst-II using refration derived keratometric values of all formulae were statistically highest.

A Phase 2 Trial of PEF ( Cispatin , Etoposide , 5-Fluorouracil ) Chemotherapy for Metastatic Stomach Cancer / 대한암학회지

PURPOSE: To determine the activity and toxicities of PEF (Cisplatin, Etoposide, 5-Fluorouracil) chemotherapy for stomach cancer. MATERIALS AND METHODS: Patients with previously untreated metastatic stomach cancer were treated with PEF regimen which consisted of cisplatin (20 mg/m2 i.v. days 1~5), etoposide (100 mg/m2 i.v. days 1, 3, 5), and 5-fluorouracil (5-FU)(800 mg/m2 i.v. infusion for 12 hours days 1~5). Chemotherapy was repeated every 3 weeks until disease progressed or toxicities were intolerable. RESULTS: Between May 1989 and July 1990, 40 patients were enrolled in this protocol. Twelve patients were lost to follow up after one cycle of chemotherapy and inevaluable. After 2~8 cycles (median 3) of chemotherapy, 20 out of 28 evaluable patients showed objective responses without any complete response, making the response rate 71% (95% confidence interval: 54~89%). The responses lasted from 4+ to 39 weeks (median: 38 weeks). The overall survival of total evaluable patients was 4+ ~50+ weeks (median 38 weeks). Among total 109 cycles of chemotherapy, cycles were delayed or doses were reduced in 48 cycles (44%) because of leukopenia (in 61 cycles: 56%) and/or thrombocytopenia (in 14 cycles: 13%). However, there was no treatment-related death. Nausea/vomiting and alopecia were experienced in most of patients. The stomatitis was experienced in 7 patients (25%) but completely reversible. In contrast, the peripheral neuropathy which developed in 4 patients (14%) after 5 cycles of chemotherapy was not reversible. CONCLUSION: The PEF regimen was active and tolerable in stomach cancer.

A Case of Constrictive Pericarditis with Localized Pericardial Effusion Simulating a Cystic Mass

Chronic constrictive pericarditis is an uncommon disease, but an importanat one because of its potential curability. It usually begins with an initial episode of acute pericarditis often with a pericardial effusion which may not be detected clinically. This then progresses to resorption of the effusion followed by obliteration of pericardial abity with formation of fibrotic tissue, which results in symmetrical scarring that produce uniform restriction. In general, there are no specific problems due to remained pericardial effusion in the clinically manifestated case of constrictive pericarditis. We report a case of chronic constrictive pericarditis with localized pericardial effusion, which caused to hemodynamic compromise due to local compression of the right ventricle.

Urinary polyamines in patients with gastrointestinal malignancy / 대한암학회지

No abstract available.