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말초혈액에서 Tg mRNA에 대한 역전사 중합효소 연쇄 반응법의 갑상선 재발암의 분자생물학적 진단
권성일,박기룡,김현영,신채희,임영찬,최영식,박요한,이강대,장희경,이재화,염하용 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.4
연구배경: 갑상선암은 다른 조직에 발생한 암에 비해 비교적 천천히 자라므로 대부분 예후가 양호하지만, 일부에서는 주위 조직으로 침윤하거나 혹은 원격 전이로 인하여 치명적인 결과를 초래할 수 있다. 갑상선전절제술 및 131^I 제거술 후 경과 관찰시 갑상선암의 재발과 전이의 진단에 있어 131^I 스캔과 혈청 Tg의 측정이 현재 임상에서 가장 많이 이용되고 있으나 이 방법에는 여러 가지의 결점이 있다. 최근 Tg mRNA에 대한 RT-PCR법을 이용한 여러 연구결과는 131^I 스캔과 혈청 Tg 측정의 결점을 보완할 수 있는 좋은 보조적인 진단법으로 이용할 수 있을 가능성을 제시하였다. 이에 말초혈액에서 측정한 Tg mRNA에 대한 RT-PCR법이 갑상선 절제술 및 방사성요드 치료 후 갑상선암의 재발 및 전이 유무의 진단에 유용한가를 알아보고자 이 연구 시행하였다. 방법: 분화된 갑상선암으로 진단된 후 갑상선전절제술을 시행받고 방사성요드 치료를 받은 환자 중 현재까지 한차례에 이상 추적 방사성요드 전신 스캔을 시행하고 추적관찰이 가능했던 유두선암 35예, 여포선암 5예를 대상으로 연구를 시행하였다. 대상군은 131^I 스캔 소견상 음성인 군(Group Ⅰ), 잔여조직이 있는 군(Group Ⅱ), 국소전이가 있는 군(Group Ⅲ), 및 원격전이 군(Group Ⅳ)으로 구분하였다. 정상 대조군은 갑상선질환이 없는 10예의 건강인으로 하였다. 대상환자의 말초혈액을 이용한 Tg mRNA에 대해 특이적인 primer를 이용하여 RT-PCR 및 nested RT-PCR을 시행하였다. 결과: 본 연구 결과는 다음과 같다. 1) 131^I 스캔 소견상 음성인 군 21예 중 1예에서 Tg가 양성소견을 보였다. Anti Tg Ab가 양성인 4예 모두 Tg가 음성을 보였다. 잔여조직이 있거나 국소전이 및 원격전이를 보인 군 19예 중 Tg가 양성인 경우는 4예였으나, Tg mRNA는 전예에서 양성이었다. 2) 131^I 스캔에서 국소 및 원격전이 소견을 보인 8예 중 4예에서 Tg가 음성으로 131^I 스캔과 혈청 Tg 사이에 불일치 소견을 보였다. 3) 말초혈액에서 특이적인 primer를 이용하여 RT-PCR 및 nested RT-PCR을 시행한 결과 대상군 40예 및 정상 대조군 10예 모두에서 Tg mRNA가 양성을 보였다. 결론: 본 연구에서 갑상선 절제술 및 방사성요드 치료 후 갑상선암의 재발 및 전이 유무를 평가함에 있어 역전사 중합효소 연쇄 반응법을 이용한 Tg mRNA 측정의 의의는 재평가되어야 한다고 생각된다. Background: Differentiated thyroid cancer is the most common endocrine malignancy. Despite advances in the treatment of thyroid cancer, disease recurrence and metastasis may occur in as many as 20% of patients, and so continues to pose major problems in its clinical management. Serum thyroglobulin (Tg) measurements, by immunoassay, are used to detect residual or recurrent thyroid cancer following thyriod ablation. However, the usefulness of immunoassay is limited by both the requirement for thyroid hormone withdrawal, to attain optimal test sensitivity, and interference by the antithyroglobulin antibody (Anti-Tg Ab). Recent studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of Tg mRNA in the peripheral blood of patients with differentiated thyroid carcinomas. We performed this study to evaluated the usefulness RT-PCR of Tg mRNA in peripheral blood of patients with thyroid carcinoma following a total thyroidectomy and radioiodine ablation therapy. Methods: Forty cases that underwent a total thyroidectomy and radioiodine ablation therapy were included in this study. Of the 40 patients, 35 were papillary carcinomas and 5 were follicular carcinomas. Ten normal control subjects were also studied. Tg mRNA was extracted. Then RT-PCR and nested RT-PCR, were run with specific Tg primers. Concurrently, DNA sequencing of the isolates was carried out to prove the isolates were identical to the nucleotide sequence of the Tg. Results: The Tg was detected in 4 of 19 patients, with either a residual thyroid bed, or metastasis, on a 131^I whole body scan and in 1 of 21 patients with a negative radioiodine scan. Surprisingly, the Tg mRNA was detected in all the patients and normal controls. Conclusion: From our results we can not recommend Tg mRNA, detected by RT-PCR in peripheral blood, as a tumor marker superior to that of the Tg serum level. We consider an intensive re-evaluation of the method is required before considering its clinical applications (J Kor Soc Endocrinol 17:501∼513, 2002).
Kwon Chae Hwa,Seo Hyung-Il,Kim Dong Uk,Han Sung Yong,Kim Suk,Lee Nam Kyung,Hong Seung Baek,Ahn Ji Hyun,Park Young Mok,Noh Byung Gwan 대한종양외과학회 2023 Korean Journal of Clinical Oncology Vol.19 No.1
Purpose: Resectable pancreatic ductal adenocarcinoma (PDAC) has a high risk of recurrence after curative resection; despite this, the preoperative risk factors for predicting early recurrence remain unclear. This study therefore aimed to identify preoperative inflammation and nutrition factors associated with early recurrence of resectable PDAC.Methods: From March 2021 to November 2021, a total of 20 patients who underwent curative resection for PDAC were enrolled in this study. We evaluated the risk factors for early recurrence within 1 year by univariate and multivariate analyses using Cox hazard proportional regression. The cutoff values for predicting recurrence were examined using receiver operating characteristic (ROC) curves.Results: In our univariate and multivariate analyses, C-reactive protein (CRP), CRP-albumin ratio, and CRP-prealbumin ratio, as well as sex and age, were significant independent prognostic factors for early recurrence in PDAC. However, known inflammatory factors (neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios), nutritional factors (albumin, prealbumin, ferritin, vitamin D), and inflammatory-nutritional factors (Glasgow Prognostic Score, modified Glasgow Prognostic Score, albumin-bilirubin) showed no association with early recurrence. In addition, using cutoff values by ROC curve analysis, a high preoperative CRP level of >5 mg/L, as well as high CRP-to-albumin (>5.3) and CRP-to-prealbumin (>1.3) ratios showed no prognostic value.Conclusion: Our results showed that inflammatory and perioperative nutritional factors, especially CRP-to-prealbumin ratio, have significant associations with early recurrence after curative resection in resectable PDAC. Therefore, for such patients, a cautious approach is needed when inflammation and poor nutritional status are present.
Kwon, Dong-Yeul,Kang, Ok Hwa,Choi, Jang-Gi,Lee, Young-Seob,Oh, Yoo-Chang,Chae, Hee-Sung,Lee, Go-Hoon,Park, Pil-Sang,Kim, Youn-Chul,Sohn, Dong Hwan,Park, Hyun,Lee, John Hwa INVERNI DELLA BEFFA 2007 Fitoterapia Vol.78 No.6
<P><B>Abstract</B></P><P>Methanol extract and its fractions (hexane, EtOAc, <I>n</I>-BuOH, and H<SUB>2</SUB>O) of <I>Dryopteris crassirhizoma</I> were investigated for antibacterial activity against methicillin-resistant <I>Staphylococcus aureus.</I> The hexane fraction showed a good antibacterial activity against all tested strains.</P>
Chae, Hee-Sung,Kang, Ok-Hwa,Choi, Jang-Gi,Oh, You-Chang,Lee, Young-Seob,Jang, Hye-Jin,Kim, Jong Hak,Park, Hyun,Jung, Kyu Yong,Sohn, Dong Hwan,Kwon, Dong-Yeul Pharmaceutical Society of Japan 2009 Biological & pharmaceutical bulletin Vol.32 No.4
<P>In this study, we evaluated the effect of 5-hydroxytryptophan on anti-inflammatory and analgesic activity in RAW 264.7 cells. Cells were treated with different concentrations of 5-hydroxytryptophan for either 1 h or for 24 h. The anti-inflammatory effect was then analyzed by enzyme-linked immunosorbent assay (ELISA), Western blotting and reverse transcription polymerase chain reaction (RT-PCR). In addition, the analgesic activity was evaluated by measuring the acetic acid-induced writhing response. We found that 5-hydroxytryptophan significantly reduced the acetic acid-induced writhing response. Moreover we evaluated the effects of 5-hydroxytryptophan on the release of several inflammatory mediators including nitric oxide (NO) and interleukin-6 (IL-6). Our results demonstrated that 5-hydroxytryptophan inhibited the lipopolysaccharide (LPS)-induced expression of NO and IL-6. Furthermore, we found that 5-hydroxytryptophan played a role in LPS induced inducible nitric oxide synthase (iNOS), cyclo oxygenase-2 (COX-2) and extracellular-signal regulated protein kinase (ERK) activation. Taken together, these results indicate that 5-hydroxytryptophan has the potential for use in the treatment of inflammatory disease and as an analgesic.</P>
Chae, Jung-Woo,Yun, Hwi-yeol,Eom, Han Young,Jeong, Eun Ju,Koo, Tae-Sung,Kwon, Kwang-il,Lee, Jong-Hwa Elsevier 2017 Journal of chromatography. B, Analytical technolog Vol.1061 No.-
<P><B>Abstract</B></P> <P>CKD-712 is a potential treatment for sepsis, as it exhibits protective effects against lipopolysaccharide-mediated platelet aggregation, inducible nitric oxide synthase expression, and cecum-ligation puncture-induced septic mortality in mice. In this study, we develop a rapid and sensitive LC–MS/MS method for determining CKD-712 in rat plasma. CKD-712 and papaverine hydrochloride (an internal standard) were analyzed using an LC–MS/MS system consisting of an Agilent HPLC system (HP-1100) equipped with an Atlantis HILIC Silica (2.1×50mm, 3μm) column and a API 4000 (Applied Biosystems/MDS Sciex, USA) in a positive ESI mode. We utilized multiple reaction monitoring (MRM) at <I>m</I>/<I>z</I> transitions of 306.2–164.0 to analyze CKD-712, and 340.3–202.1 <I>m</I>/<I>z</I> for IS, with a mobile phase of acetonitrile (0.025% trifluoroacetic acid):20mM ammonium acetate (94:6, v/v) at a flow rate of 0.25mL/min. The lower limit of quantification (LLOQ) was 5ng/mL, with a linearity ranging from 5 to 1000ng/mL (<I>r </I>>0.999). Validation parameters including specificity, precision, accuracy, matrix effect, recovery, dilution effect and stability results were well within acceptance criteria, and applied successfully on a pharmacokinetic study in rats.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CKD-712 is a drug candidate on stage of clinical trial for the treatment of sepsis. </LI> <LI> LC–MS/MS assay for determining CKD-712 levels in rat plasma was established and validated. </LI> <LI> This method is the simple preparation procedure, which results in adequate recovery. </LI> </UL> </P>