• 생명과학회지
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• 제28권6호
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• pp.753-763
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• 2018

Cathepsin은 리소좀에 존재하는 효소로, 엔도좀-리소좀 경로를 통하여 손상된 단백질의 분해를 유도한다. 이러한 cathepsin은 활성화되는 촉매 잔기 위치(catalytic residue site)에 따라 cysteine, aspartate, serine cathepsin으로 나뉜다. 다양한 암세포에서 cysteine cathepsin은 유전자 증폭이나 전사, 번역, 전사 후 단계를 통해 높은 발현을 유지한다. 특히 cathepsin S의 경우, 다른 cysteine cathepsin과 달리 중성 pH 환경에서도 안정적으로 활성도를 유지하며 특정 조직에서 발현이 제한적이라는 특징을 가지고 있기 때문에 질병의 미세환경에서 중요한 역할을 한다. 면역세포에서의 cathepsin S는 불변 사슬(invariant chain)을 분해하여 항원 제시에 중요한 MHC class II의 활성화를 통해 면역 반응을 조절하며, 암세포에서의 cathepsin S는 전이와 혈관신생을 조절함으로써 암세포의 성장을 증가시키는 역할을 한다. Cathepsin S의 발현 조절에 문제가 생기면 암, 관절염, 심혈관 질환을 포함한 많은 병리학적 현상에 영향을 미친다. 특히 암세포에서 cathepsin S의 발현 억제와 결함은 혈관신생을 억제시킬 뿐만아니라, 암세포의 성장과 전이를 감소시키고 세포사멸을 유도한다. 따라서, cathepsin S는 암 치료에 있어 좋은 표적이 될 수 있다.

• Tuberculosis and Respiratory Diseases
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• 제49권4호
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• pp.502-507
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• 2000

저자들은 기관지 원성 폐암이 의심되었으나 기관지 내시경 검사 및 전립선 종물 조직검사상 전립선암의 기관지내 전이가 증명되었고 호르몬 치료 후 방사선 소견 및 PSA 추적 검사성 호전 소견을 보인 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• Molecules and Cells
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• 제26권1호
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• pp.5-11
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• 2008

Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is catalyzed by Rad6/Rad18 complex. PCNA monoubiquitination triggers the replacement of replicative polymerase with special translesion synthesis (TLS) polymerases that are able to replicate past DNA lesions. The PCNA interaction motif and/or the ubiquitin binding motif in most TLS polymerases seem to be important for the regulation of TLS. The TLS pathway is usually error-prone because TLS polymerases have low fidelity and no proofreading activity. PCNA can also be further polyubiquitinated by Ubc13/ Mms2/Rad5 complex, which adds an ubiquitin chain onto monoubiquitinated K164 of PCNA. PCNA polyubiquitination directs a different PRR pathway known as error-free damage avoidance, which uses the newly synthesized sister chromatid as a template to bypass DNA damage presumably through template switching mechanism. Mammalian homologues of all of the yeast PRR proteins have been identified, thus PRR is well conserved throughout evolution. Mutations of some PRR genes are associated with a higher risk for cancers in mice and human patients, strongly supporting the importance of PRR as a tumor suppressor pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제23권2호
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• pp.103-111
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• 2019

The study is to investigate effects of andrographolide on experimental autoimmune myocarditis (EAM). Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The EAM rats were treated with either andrographolide (25, 50, 100 mg/kg/day) or vehicle for 21 days. An antigen-specific splenocytes proliferation assay was performed by using the cells from control rats immunized with cardiac myosin. Survival rates, myocardial pathology and myocardial functional parameters (left ventricle end-diastolic pressure, ${\pm}dP/dt$ and left ventricular internal dimension) of EAM rats received andrographolide were significantly improved. Andrographolide treatment caused an decrease in the infiltration of $CD3^+$ and $CD14^+$ positive cells in myocardial tissue. Moreover, andrographolide treatment caused a reduction in the plasma levels of tumor necrosis factor-alpha, interleukin-17 (IL-17) and myosin-antibody, and an increase in the level of IL-10 in EAM rats. Oral administration of andrographolide resulted in the decreased expression of p-PI3K, p-Akt without any change of PI3K and Akt. Further results indicate andrographolide significantly inhibited myosin-induced proliferation in splenocytes, and this effect was inhibited by co-treatment of SC79 (Akt activator). Our data indicate andrographolide inhibits development of EAM, and this beneficial effect may be due to powerful anti-inflammatory activity and inhibitory effect on PI3K/Akt pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3075-3078
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• 2013

Background: KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkers in the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4 signaling plays important roles in the development of PCa. However, associations of these genes with PCa in northern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence and level of malignancy. Methods: All subjects were from Beijing and Tianjin, including 266 cases with prostate cancer and 288 normal individuals as controls. We evaluated associations between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score, tumor stage and aggressive) and 6 candidate PCa risk loci, genotyped by PCR- high resolution melting curve and sequencing methods. Results: Case-control analysis of allelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6 gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval (CI) =0.57-0.94, P = 0.013) in northern Chinese men. In addition, subjects with CX (CC+TC) genotypes had a decreased risk for prostrate cancer compared to those carrying the TT homozygote (OR =0.64, 95% CI = 0.45- 0.90, P = 0.008). The TT genotype of 13q22 (rs9600079, T) was associated with tumor stage (P=0.044, OR=2.34, 95% CI=0.94-5.87). Other SNPs were not significantly associated with clinical covariates in prostate cancer (P > 0.05). Conclusions. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locus in northern Chinese men.

• 한국식품영양과학회지
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• 제40권12호
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• pp.1662-1667
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• 2011

안토시아닌(anthocyanins)은 플라보노이드에 속하고 항산화 활성들을 포함한 그들의 다양한 건강 유익성에 대해 알려져 있다. 그들 중 검정콩 껍질에서 분리한 주요 안토시아닌은 glycopyranose를 함유하고 있는 배당체이다. 천식은 호염기성 세포(basophils)와 비만세포(mast cells)를 포함한 다양한 면역세포와 관련된 알레르기 관련 질병이다. 호산구(eosinophils), 호염기성 세포, 비만세포는 탈과립화에 의한 천식-특이적 보조 2(T-helper 2) 사이토카인 분비 그리고 계속해서 일어나는 증폭과 같은 염증을 일으키는 매개체의 증가를 통해 알레르기 천식(allergic asthma)에서 중요한 역할을 한다. 흰쥐 호염기성 백혈병(rat basophilic leukemia) RBL-2H3 세포는 알레르기 반응을 측정하기 위해 가장 일반적으로 사용되는 in vitro 모델이다. 본 연구에서는 검정콩 껍질 안토시아닌이 항원으로 자극한 RBL-2H3 세포에서 탈 과립 그리고 Th2 사이토카인 생산에 미치는 효과를 조사하였다. 세포 탈과립은 ${\beta}$-hexosaminidase의 방출을 검출함으로써 평가하였다. IgE-항원 복합체로 자극한 RBL-2H3 세포내 ${\beta}$-hexosaminidase 방출과 Th2 사이토카인 생산이 무처리군의 그것과 비교하여 더 높았다. 안토시아닌은 RBL-2H3 세포의 IgE-항원 복합체 유도 탈과립을 현저하게 억제시켰고 RBL-2H3 세포내 IgE-항원 복합체-매개체 interleukin(IL)-4, IL-13 그리고 TNF-${\alpha}$ 생산을 저해하였다. 이러한 결과는 검정콩 껍질 유래 안토시아닌이 알레르기 반응(allergic reaction)을 현저히 저해하는 효과가 있음을 보였고, 이들 안토시아닌이 향후 알레르기 천식을 억제하거나 개선하는데 유용한 물질로 사용될 가능성이 있을 것으로 판단되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8177-8182
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• 2014

Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

• Tuberculosis and Respiratory Diseases
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• 제47권5호
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• pp.691-696
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• 1999

건강검진시 촬영한 단순흉부사진에서 우연히 발견된 다발성 결절로 내원한 34세 여자 환자에서 개흉술을 통한 조직검사상 미분화 혈관분화를 보이고 면역조직 화학염색상 제 VIII 인자-관련인자, CD34 와 vimentin에 양성반응을 보여 EH로 확진 되었던 1예를 경험하였기에 보고하는 바이다.

• 대한한방내과학회지
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• 제39권5호
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• pp.973-983
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• 2018

Objectives: We report a case of traditional Korean medicine (TKM) treatment for skin side effects after taking afatinib (Giotrif$^{(R)}$). Methods: A 62-year-old female who was diagnosed with non-small cell lung cancer stage 4 (T4N2M1b) and was on treatment with afatinib (29.56 mg/day for 4 months) complained of skin toxicity as a side effect. For 16 admission days, the patient was treated with acupuncture, moxibustion, and herbal medicine (oral decoction and external ointment). Results: Improvement of skin toxicity was measured by a numeric rating scale. In addition, Quality of life (QOL) was measured using EORTC Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire, 13-item lung cancer-specific module (EORTC QLQ-LC13) Developed by the European Organization for Research and Treatment of Cancer (EORTC). Tumor size and carcinoembryonic antigen (CEA) were also examined during follow up. Conclusions: After a combined TKM treatment, skin toxicity symptoms and quality of life scales were significantly improved with no side effects. The tumor size was not changed on computed tomography during follow-up period. CEA levels were decreased.

• Korean Journal of Radiology
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• 제25권2호
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.