• Title/Summary/Keyword: therapeutic potential

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Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer

  • Hyeran Shim;Kiwon Jang;Yeong Hak Bang;Hoang Bao Khanh Chu;Jisun Kang;Jin-Young Lee;Sheehyun Cho;Hong Seok Lee;Jongbum Jeon;Taeyeon Hwang;Soobok Joe;Jinyeong Lim;Ji-Hye Choi;Eun Hye Joo;Kyunghee Park;Ji Hwan Moon;Kyung Yeon Han;Yourae Hong;Woo Yong Lee;Hee Cheol Kim;Seong Hyeon Yun;Yong Beom Cho;Yoon Ah Park;Jung Wook Huh;Jung Kyong Shin;Dae Hee Pyo;Hyekyung Hong;Hae-Ock Lee;Woong-Yang Park;Jin Ok Yang;Young-Joon Kim
    • BMB Reports
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    • v.57 no.2
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    • pp.110-115
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    • 2024
  • Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator Phenotype-High (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the methylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC.

Initial Experience of the Emergency Bypass System ($EBS^{(R)}$) for the Patients with Cardiogenic Shock due to an Acute Myocardial Infarction (급성 심근경색으로 인한 심인성 쇼크 환자에 대한 경피적 순환 보조장치($EBS^{(R)}$) 적용의 초기경험)

  • Ryu, Kyoung-Min;Kim, Sam-Hyun;Seo, Pil-Won;Ryu, Jae-Wook;Kim, Seok-Kon;Kim, Young-Hwa;Park, Seong-Sik
    • Journal of Chest Surgery
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    • v.41 no.3
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    • pp.329-334
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    • 2008
  • Background: Percutaneous cardiopulmonary support. (PCPS) has the potential to rescue patients in cardiogenic shock who might otherwise die. PCPS has been a therapeutic option in a variety of the clinical settings such as for patients with myocardial Infarction, high-risk coronary intervention and postcardiotomy cardiogenic shock, and the PCPS device is easy to install. We report our early experience with PCPS as a life saving procedure in cardiogenic shock patients due to acute myocardial infarction. Material and Method: From January 2005 to December 2006, eight patients in cardiogenic shock with acute myocardial infarction underwent PCPS using the CAPIOX emergency bypass system($EBS^{(R)}$, Terumo, Tokyo, Japan). Uptake cannulae were inserted deep into the femoral vein up to the right atrium and return cannulae were inserted into the femoral artery with Seldinger techniques using 20 and 16-French cannulae, respectively. Simultaneously, autopriming was performed at the $EBS^{(R)}$ circuit. The $EBS^{(R)}$ flow rate was maintained between $2.5{\sim}3.0L/min/m^2$ and anticoagulation was performed using intravenous heparin with an ACT level above 200 seconds. Result: The mean age of patients was $61.1{\pm}14.2$ years (range, 39 to 77 years). Three patients were under control of the $EBS^{(R)}$ before percutaneous coronary intervention (PCI), three patients were under control of the $EBS^{(R)}$ during PCI, one patient was under control of the $EBS^{(R)}$ after PCI, and one patient was under control of the $EBS^{(R)}$ after coronary bypass surgery. The mean support time was $47.5{\pm}27.9$ hours (range, 8 to 76 hours). Five patients (62.5%) could be weaned from the $EBS^{(R)}$ after $53.6{\pm}27.2$ hours. (range, 12 to 68 hours) of support. All of the patients who could successfully be weaned from support were discharged from the hospital. There were three complications: one case of gastrointestinal bleeding and two cases of acute renal failure. Two of the three mortality cases were under cardiac arrest before $EBS^{(R)}$ support, and one patient had an intractable ventricular arrhythmia during the support. All of the discharged patients are still surviving at $16.8{\pm}3.1$ months (range, 12 to 20 months) of follow-up. Conclusion: The use of $EBS^{(R)}$ for cardiogenic shock caused by an acute myocardial infarction could rescue patients who might otherwise have died. Successfully recovered patients after $EBS^{(R)}$ treatment have survived without severe complications. More experience and additional clinical investigations are necessary to elucidate the proper installation timing and management protocol of the $EBS^{(R)}$ in the future.

Inhibition of Neointima Formation and Migration of Vascular Smooth Muscle Cells by Anti-vascular Endothelial Growth Factor Receptor-1 (Flt-4) Peptide in Diabetic Rats (당뇨병 쥐에서 혈관내피 성장인자 수용체-1 차단 펩타이드를 이용한 신내막 형성과 혈관평활근세포 이동의 억제)

  • Jo, Min-Seop;Yoo, Ki-Dong;Park, Chan-Beom;Cho, Deog-Gon;Cho, Kue-Do;Jin, Ung;Moon, Kun-Woong;Kim, Chul-Min;Wang, Young-Pil;Lee, Sun-Hee
    • Journal of Chest Surgery
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    • v.40 no.4 s.273
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    • pp.264-272
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    • 2007
  • Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

Effect of Boswellia serrata Extracts on Degenerative Osteoarthritis in vitro and in vivo Models (보스웰리아 추출물의 골관절염 억제 효과 연구)

  • Nam, Da-Eun;Kim, Ok Kyung;Shim, Tae Jin;Kim, Ji Hoon;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.5
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    • pp.631-640
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    • 2014
  • The inhibitory effects of Boswellia serrata (BW) extracts on degenerative osteoarthritis were investigated in primary-cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. To identify the protective effects of BW extract against $H_2O_2$ ($800{\mu}M$, 2 hr) in vitro, cell survival was measured by MTT assay. Cell survival after $H_2O_2$ treatment was elevated by BW extract at a concentration of $20{\mu}g/mL$. In addition, BW extract treatment significantly reduced and normalized the productions of pro-inflammatory factors, nuclear transcription factor ${\kappa}B$, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 at a concentration of $20{\mu}g/mL$. Treatment of chondrocytes with BW extract significantly reduced 5-lipoxygenase activity and production of prostaglandin E2, especially at a concentration of $10{\sim}20{\mu}g/mL$. For the in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. Consumption of a diet containing BW extract (100 and 200 mg/kg) for 35 days significantly inhibited the development and severity of osteoarthritis in rats. To determine the genetic expression of arthritic factors in articular cartilage, real-time PCR was applied to measure matrix metalloproteinases (MMP-3, MMP-9, and MMP-13), collagen type I, collagen type II, and aggrecan, and BW extract had protective effects at a concentration of 200 mg/kg. In conclusion, BW extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and chondrocyte injury. One can consider that BW extract may be a potential therapeutic treatment for degenerative osteoarthritis.

Therapeutic Results of Radiotherapy in Rectal Carcinoma - Comparison of Sandwich Technique Radiotherapy with Postoperative Radiotherapy (직장암의 방사선 치료 결과 - Sandwich Technique 방사선 치료와 수술후 방사선 치료의 비교)

  • Huh Cil Cha;Suh Hyun Suk;Lee Hyuk Sang;Kim Re Hwe;Kim Chul Soo;Kim Hong Yong;Kim Sung Rok
    • Radiation Oncology Journal
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    • v.14 no.1
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    • pp.25-31
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    • 1996
  • Purpose : To evaluate the potential advantage for 'sandwich' technique radiotherapy compared to Postoperative radiotherapy in resectable rectal cancer. Materials and Methods : Between January 1989 and Mar 1994, 60 patients with resectable rectal cancer were treated at Inje University Seoul and Sanggye Paik Hospital. Fifty one patients were available for analysis: 20 patients were treated with sandwich technique radiotherapy and 31 patients were treated with Postoperative radiotherapy. In sandwich technique radiotherapy(RT), Patients were treated with preoperative RT 1500 cGy/5fx, followed by immediate curative resection. Patients staged as Astler-Coiler B2, C were considered for postoperative RT with 2500-4500 cGy. in postoperative RT total radiation dose of 4500-6120 cGy, 180 cGy daily at 4-Sweets was delivered. Patients were followed for median period of 25 months. Results : The overall 5-year survival rates for sandwich RT group and postoperative RT group were $60\%$ and $71\%$, respectively(p>0.05). The 5-rear disease free survival rates for each group were $63\%$. There was no difference in local failure rate between two groups($11\%$ versus $7\%$) Incidence of distant metastasis was $11\%$(2/20) in the sandwich technique RT group and $20\%$(6/31) in the postoperative RT group(p>0.05). The frequencies of acute and chronic complications were comparable in both groups. Conclusion : The sandwich technique radiotherapy group shows local recurrence and survival similar to those of Postoperative RT alone group but reduced distant metastasis compared to Postoperative RT group. But long term follow-up and large number of patients is needed to make an any firm conclusion regarding the value of this sandwich technique RT.

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