• Title/Summary/Keyword: Receptor-based approach

Search Result 56, Processing Time 0.253 seconds

Pathway Crosstalk Analysis Based on Protein-protein Network Analysis in Ovarian Cancer

  • Pan, Xiao-Hua
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.8
    • /
    • pp.3905-3909
    • /
    • 2012
  • Ovarian cancer is the fifth leading cause of cancer death in women aged 35 to 74 years. Although there are several popular hypothesis of ovarian cancer pathogenesis, the genetic mechanisms are far from being clear. Recently, systems biology approaches such as network-based methods have been successfully applied to elucidate the mechanisms of diseases. In this study, we constructed a crosstalk network among ovarian cancer related pathways by integrating protein-protein interactions and KEGG pathway information. Several significant pathways were identified to crosstalk with each other in ovarian cancer, such as the chemokine, Notch, Wnt and NOD-like receptor signaling pathways. Results from these studies will provide the groundwork for a combination therapy approach targeting multiple pathways which will likely be more effective than targeting one pathway alone.

Prediction the efficacy and mechanism of action of Daehwangmokdanpitang to treat psoriasis based on network pharmacology (네트워크 약리학 기반 대황목단피탕(大黃牧丹皮湯)의 건선 조절 효능 및 작용 기전 예측)

  • Bitna Kweon;Dong-Uk Kim;Gabsik Yang; Il-Joo Jo
    • The Korea Journal of Herbology
    • /
    • v.38 no.6
    • /
    • pp.73-91
    • /
    • 2023
  • Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.

Rapid differentiation of Hanwoo and Holstein meat using multiplex allele specific polymerase chain reaction protocols (Multiplex allele specific PCR 방법을 이용한 한우고기와 젖소고기의 신속한 판별)

  • Koh, Ba-Ra-Da
    • Korean Journal of Veterinary Research
    • /
    • v.45 no.3
    • /
    • pp.351-357
    • /
    • 2005
  • Here I describe a multiplex allele specific PCR-based approach for the rapid detection between Hanwoo and Holstein meat associated with Melanocortin 1 receptor (MC1R) gene. Specific and universal oligonucleotide primers were used in combination to detect the presence of a single nucleotide polymorphism within the bovine MC1R DNA sequence. The presence of the bovine MC1R gene is indicated by the production of a single control PCR product, whilst positive samples generate an alternative smaller specific product over the same region. The mutations in MC1R104 codon revealed depending on the presence or absence of an indicative fragment amplified from the wild-type allele of this codon. As little as 0.39 ng and 1.56 ng of genomic DNA of Hanwoo and Holstein could be detected by MAS-PCR assay, respectively. This technique, which is widely used in human genetic screening, provides a reliable and sensitive result that has not been documented for the identification of bovine coat color. The MAS-PCR assay approach was proven to be useful in complementing routine beef DNA analysis for differentiation of these MC1R variants and it would facilitate the screening of deceiving sales of Holstein meat in the butcher shop.

A Novel Approach to the Discovery of Non-systemic Anti-inflammatory Steroids; Antedrug

  • Lee, Henry-J.;Ko, Dong-Hoon
    • Archives of Pharmacal Research
    • /
    • v.22 no.3
    • /
    • pp.279-287
    • /
    • 1999
  • Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary function and the immune system.. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents which are designed to undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation from the applied site. Thus, true antedrugs are devoid of systemic adverse effects. In a continuing effort, 16$\alpha$-carboxylate and isoxazoline derivatives of prednisolone have been synthesized and screened. In the croton oil-induced ear edema bioassay, the following relative potencies were obtained setting hydrocortisone=1.0; 3a, 1.5; 3b, 3.1; 4a, 4.0; 4b, 12.2; 5b, 8.2; 6b, 11.2; 7a, 1.9; 7b, 4.1; 8a, 3.3; 8b 6.8; 9a, 0.7; 9b 8.6; 10a 2.6; 10b, 7.4. Results of the five-day bioassay indicated that, in contrast to the parent compound, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, adrenal weights or plasma corticosterone levels. Taken together, the antedrug concept appears to be a fundamentally sound strategy for the separation of local anti-inflammatory activity form systemic adverse effects.

  • PDF

Single Interaction Force of Biomolecules Measured with Picoforce AFM (원자 힘 현미경을 이용한 단일 생분자 힘 측정)

  • Jung, Yu-Jin;Park, Joon-Won
    • Journal of the Korean Vacuum Society
    • /
    • v.16 no.1
    • /
    • pp.52-57
    • /
    • 2007
  • The interaction force between biomolecules(DNA-DNA, antigen-antibody, ligand-receptor, protein-protein) defines not only biomolecular function, but also their mechanical properties and hence bio-sensor. Atomic force microscopy(AFM) is nowadays frequently applied to determine interaction forces between biological molecules and biomolecular force measurements, obtained for example using AFM can provide valuable molecular-level information on the interactions between biomolecules. A proper modification of an AFM tip and/or a substrate with biomolecules permits the direct measurement of intermolecular interactions, such as DNA-DNA, protein-protein, and ligand-receptor, etc. and a microcantilever-based sensor appeared as a promising approach for ultra sensitive detection of biomolecular interactions.

Construction of a Preliminary Conceptual Site Model Based on a Site Investigation Report for Area of Concerns about Groundwater Contamination (지하수 오염우려지역 실태조사 보고서 기반의 사전 부지개념모델 구축)

  • Kim, Juhee;Bae, Min Seo;Kwon, Man Jae;Jo, Ho Young;Lee, Soonjae
    • Journal of Soil and Groundwater Environment
    • /
    • v.27 no.spc
    • /
    • pp.64-74
    • /
    • 2022
  • The conceptual site model (CSM) is used as a key tool to support decision making in risk based management of contaminated sites. In this work, CSM was applied in Jeonju Industrial Complex where site investigation for groundwater contamination was conducted. Site background information including facility types, physical conditions, contaminants spill history, receptor exposure, and ecological information were collected and cross-checked with tabulated checklist necessary for CSM application. The CSM for contaminants migration utilized DNAPL transport model and narrative CSMs were constructed for source to receptor pathway, ecological exposure route, and contaminants fate and transport in the form of a diagram or flowchart. The component and uncertainty of preliminary CSM were reviewed using the data gap analysis while taking into account the purpose of the survey and the site management stage at the time of the survey. Through this approach, the potential utility of CSM was demonstrated in the site management process, such as assessing site conditions and planning follow-up survey work.

CoMFA and CoMSIA on the Neuroblocking Activity of 1-(6-Chloro-3-pyridylmethyl)-2-nitroiminoimidazolidine Analogues

  • Sung, Nack-Do;Jang, Seok-Chan;Choi, Kyoung-Seop
    • Bulletin of the Korean Chemical Society
    • /
    • v.27 no.11
    • /
    • pp.1741-1746
    • /
    • 2006
  • 3D-QSARs on the neuroblocking activities by 1-(6-chloro-3-pyridylmethyl)-2-nitroiminoimidazolidine analogues as agonist at the nicotinic acetylcholine receptor (nAChR) were studied quantitatively using CoMFA and CoMSIA methodologies. The statistical results of CoMFA (A5: $r^2\;_{cv.}\;=\;0.707\;&\;r^2\;_{ncv.}$= 0.986) and CoMSIA model (A3: $r^2\;_{cv.}$ = 0.715 & $r^2\;_{ncv.}$ = 0.961) showed the best predictability and fitness for neuroblocking activity based on the cross-validated value and non-cross validated value. The steric and H-bond acceptor nature of a compound were essential for high activity. The study on 3D-QSARs between substrate molecules and their neuroblocking activities appears to be an useful approach for designing better neuroblocking drug development.

Biopsy and Mutation Detection Strategies in Non-Small Cell Lung Cancer

  • Jung, Chi Young
    • Tuberculosis and Respiratory Diseases
    • /
    • v.75 no.5
    • /
    • pp.181-187
    • /
    • 2013
  • The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.

Expression of Bradykinin Binding Sites within the Mammalian Kidney Tissues (신장 조직의 브라디키닌 결합부위 발현)

  • Chung, Sung-Hyun;Jung, Jee-Chang
    • YAKHAK HOEJI
    • /
    • v.38 no.5
    • /
    • pp.602-607
    • /
    • 1994
  • Based upon the previous experiments showing that kidney and lung tissues of rat had relatively abundant bradykinin binding sites, we tried to characterize and determine the densities of the bradykinin binding sites in the rabbit kidney tissue and proximal tubular cells under different growing conditions. Among the kidney tissue renal medulla segments showed the highest bradykinin binding sites. To determine which growth factors are to add in the serum free culture medium to express selectively the bradykinin binding sites in the rabbit kidney proximal tubular cells, we tried so called hormone-deletion approach and in here insulin, hydrocortisone, transferrin, triiodothyronine and prostaglandin $E_1$ are examined. By performing receptor binding assay and determination of protein concentrations, we may conclude that the most required hormones in the expression for bradykinin binding sites are insulin and transferrin, and fetal bovine serum is shown to be less effective in this regard.

  • PDF

Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

  • Duman, Berna Bozkurt;Afsar, Cigdem Usul;Gunaldi, Meral;Sahin, Berksoy;Kara, I. Oguz;Erkisi, Melek;Ercolak, Vehbi
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.8
    • /
    • pp.4119-4123
    • /
    • 2012
  • Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.