• Title/Summary/Keyword: Receptor status

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Effects of $17{\beta}$-Estradiol and Estrogen Receptor Antagonists on the Proliferation of Gastric Cancer Cell Lines

  • Kim, Myung-Jin;Cho, Sung-Il;Lee, Kun-Ok;Han, Hyung-Joon;Song, Tae-Jin;Park, Seong-Heum
    • Journal of Gastric Cancer
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    • v.13 no.3
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    • pp.172-178
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    • 2013
  • Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

Epidermal Growth Factor Receptor Mutations in Japanese Men with Lung Adenocarcinomas

  • Tomita, Masaki;Ayabe, Takanori;Chosa, Eiichi;Kawagoe, Katsuya;Nakamura, Kunihide
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10627-10630
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    • 2015
  • Background: Epidermal growth factor receptor (EGFR) mutations play a vital role in the prognosis of patients with lung adenocarcinoma. Such somatic mutations are more common in women who are non-smokers with adenocarcinoma and are of Asian origin. However, to our knowledge, there are few studies that have focused on men. Materials and Methods: One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. Results: EGFR mutations were positive in 48.9% and negative (wild type) in 51.1%. Overall mutation was significant in women (66.0% vs. 32.2%) compared with men (p<0.001). For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure or mixed ground-glass nodule type on computed tomography and smoking status. However, in men, EGFR mutation status was only associated with lepidic dominant histologic subtype and not the other variables. Interestingly, the Brinkman index of men with mutant EGFR also did not differ from that for the wild type ($680.0{\pm}619.3$ vs. $813.1{\pm}552.1$ p=0.1077). Conclusions: The clinical characteristics of men with lung adenocarcinoma related to EGFR mutation are not always similar to that of overall patients. Especially we failed to find the relationship between EGFR mutations and smoking status in men.

Radiotracer Methods for Targeted Imaging of the Epidermal Growth Factor Receptor (Epidermal Growth factor 수용체 영상을 위한 방사성추적자 기술)

  • Jung, Kyung-Ho;Lee, Kyung-Han
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.3
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    • pp.185-191
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    • 2008
  • While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (lressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

Generation of a monoclonal anti-human $\beta$2-adrenergic receptor antibody using GST-$\beta$-adrenergic receptor C-terminal fusion proteins expressed in E.Coli.

  • Kang, Suk-Jo;Shin, Chan-Young;Park, Kyu-Hwan;Ko, Kwang-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.95-95
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    • 1997
  • Among the various receptor molecules discovered so far the ${\beta}$2-adrenergic receptors have been regarded as excellent model systems for the so called 7 transmembrane helix receptor and have been the focus of extensive studies. For the analysis of receptor structure and function a monoclonal antibody plays a crucial role, thus providing useful tools for the study of receptor. However, because of the minute quantity of receptor molecules which could be obtained from natural sources, the generation of specific monoclonal antibody against receptor molecules from the purified receptors has been regarded as virtually impractical in consideration of cost and experimental times. The purpose of the present study was to generate and characterize a monoclonal antibody against human ${\beta}$2-adrenergic receptor. For the production of antibody, C-terminal regions of the human ${\beta}$2-adrenergic receptor was produced as a fusion protein with Glutathion S-transferase (GST) in E. Coli. The expression of the fusion protein was identified by SDS-PAGE and Western blot using monoclonal anti-GST antibody. The fusion protein was purified to an apparent homogeniety by affinity chromatography with Glutathion Sepharose CL-4B and used as an antigen for the immunization of BALB/C mice. The Production of monoclonal antibody was achieved by fusion of the immunized spleen cells and SP/2-0 myeloma cells. Positive hybridomas were screened by ELISA and were cloned by two consecutive rounds of limiting dilution. The monoclonal antibody produced in this study (mAb${\beta}$C02) was IgM type and purified by immunoaffinity chromatography using anti-mouse IgM agarose as an affinity matrix. MAb${\beta}$C02 showed strong and specific immunoreactivity against both the fusion protein and human ${\beta}$2-adrenergic receptor in ELISA and Western blot. The molecular weight of immunoreactive band was 64 kDa and exactly coincided with the previously reported molecular weight of ${\beta}$2-adrenergic recepters. The results of the present study suggest that mAb${\beta}$C02 may be used for the study of receptor function and regulation in normal or nonphysiological status.

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Iron Nutritional Status of Infants and Young Children in the Seoul Area

  • Um, Sung-Sin;Ahn, Hong-Seok;Kim, Soon-Ki;Ha, Jung-Hun
    • Journal of Community Nutrition
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    • v.4 no.1
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    • pp.3-11
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    • 2002
  • The purpose of this study is to evaluate the iron nutritional status by investigating dietary intake and analyzing the hematological iron status indices including serum transferrin receptor (sTfR) in 8 to 28 month old infants md young children taking supplementary foods. The nutrient intake of 60 healthy infants and young children from 8 to 24 months of age was investigated by means of a 24-hour recall method, and the subjects were divided into 2 groups (8- 12 months and 13-28 months) according to age. Venous blood samples from these groups were collected and measured for the following : hemoglobin(Hb), hematocrit(Hct) , mean corpuscular volume (MCV), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (MCHC), serum ferritin, serum iron, total iron binding capacity (TIBC), and sTfR. Anemia is defined as hemoglobin < 11g /dl , serum ferritin level < 10ng1m1 for iron deficiency , serum transferring receptor(sTfR) > 4.5mg / 1 for iron deficient erythropoiesis. Total daily calorie intake was 934.6 ${\pm}$ 284.5kcal (98.32% of RDA) on average. Average daily iron intake in infants aged 8 to 12 months was 8.92 ${\pm}$ 3.32mg. The mean daily iron intake in infants aged 13 to 28 months was 7.15 ${\pm}$ 3.35mg (90% of Recommended Dietary Allowance, RDA). Mean values for Hb, Hct sew ferritin and sTfR were 12.10 ${\pm}$ 0.77g141,36.02 ${\pm}$ 2.31%,20.91 ${\pm}$ 11.58ng/m1 and 3.78 ${\pm}$ 1.47mg /1, respectively. In the young children from 13 to 28 months of age, the prevalence of anemia was 5.6%. The prevalence of iron deficiency was 9.5% in those from 8 to 12 months of age, and 27.8% in those from 13 to 28 months of age. The prevalence of iron deficient erythropoiesis was 16.7% in infants aged 8 to 12 months and 44.4% in those aged 13 to 28 months. The prevalence of both serum ferritin level < 10ng/m1 sTfR > 4.5mg/1 was 22% in the young children aged 13 to 28 months. The measureand ment of sTfR may be a promising new tool in diagnosis of iron deficiency in early childhood when the iron deficiency is prevalent. It seems appropriate to emphasize nutritional education and evaluation to promote the iron nutritional status of infants and young children.

Ginsenosides Inhibit NMDA Receptor-Mediated Epileptic Discharges in Cultured Hippocampal Neurons

  • Kim, Sun-Oh;Rhim, Hye-Whon
    • Archives of Pharmacal Research
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    • v.27 no.5
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    • pp.524-530
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    • 2004
  • Epilepsy or the occurrence of spontaneous recurrent epileptiform discharges (SREDs, seizures) is one of the most common neurological disorders. Shift in the balance of brain between excitatory and inhibitory functions due to different types of structural or functional alterations may cause epileptiform discharges. N-Methyl-D-aspartate (NMDA) receptor dysfunctions have been implicated in modulating seizure activities. Seizures and epilepsy are clearly dependent on elevated intracellular calcium concentration ([C $a^{2+}$]$_{i}$ ) by NMDA receptor activation and can be prevented by NMDA antagonists. This perturbed [C $a^{2+}$]$_{i}$ levels is forerunner of neuronal death. However, therapeutic tools of elevated [C $a^{2+}$]$_{i}$ level during status epilepticus (SE) and SREDs have not been discovered yet. Our previous study showed fast inhibition of ginseng total saponins and ginsenoside R $g_3$ on NMDA receptor-mediated [C $a^{2+}$]$_{i}$ in cultured hippocampal neurons. We, therefore, examined the direct modulation of ginseng on hippocampal neuronal culture model of epilepsy using fura-2-based digital $Ca^{2+}$ imaging and neuronal viability assays. We found that ginseng total saponins and ginsenoside R $g_3$ inhibited $Mg^{2+}$ free-induced increase of [C $a^{2+}$]$_{i}$ and spontaneous [C $a^{2+}$]$_{i}$ oscillations in cultured rat hippocampal neurons. These results suggest that ginseng may playa neuroprotective role in perturbed homeostasis of [C $a^{2+}$]$_{i}$ and neuronal cell death via the inhibition of NMDA receptor-induced SE or SREDs.d SE or SREDs..

Lack of Prognostic Value of Human Epidermal Growth Factor- Like Receptor 2 Status in Inflammatory Breast Cancer (IBC): a Meta-analysis

  • Li, Xiu-Juan;Zha, Quan-Bin;Xu, Xin-Yu;Xia, Lei;Zhang, Zhe;Ren, Zhao-Jun;Tang, Jin-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9615-9619
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    • 2014
  • Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.

Cyclooxygenase-2 Expression in Invasive Breast Carcinomas of No Special Type and Correlation with Pathological Profiles Suggest a Role in Tumorigenesis Rather than Cancer Progression

  • Misron, Nurul Akmar;Looi, Lai-Meng;Mustapha, Nik Raihan Nik
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1553-1558
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    • 2015
  • Background: COX-2 has been shown to play an important role in the development of breast cancer and increased expression has been mooted as a poor prognostic factor. The purpose of this study was to investigate the relationship between COX-2 immunohistochemical expression and known predictive and prognostic factors in breast cancer in a routine diagnostic histopathology setting. Materials and Methods: Formalin-fixed paraffin-embedded tumour tissue of 144 no special type (NST) invasive breast carcinomas histologically diagnosed between January 2009 and December 2012 in Hospital Sultanah Bahiyah, Alor Setar, Kedah were immunostained with COX-2 antibody. COX-2 overexpression was analysed against demographic data, hormone receptor status, HER2-neu overexpression, histological grade, tumour size and lymph node status. Results: COX-2 was overexpressed in 108/144 (75%) tumours and was significantly more prevalent (87%) in hormone receptor-positive tumours. There was no correlation between COX-2 overexpression and HER2/neu status. Triple negative cancers had the lowest prevalence (46%) (p<0.05). A rising trend of COX-2 overexpression with increasing age was observed. There was a significant inverse relationship with tumour grade (p<0.05), prevalences being 94%, 83% and 66% in grades 1, 2 and 3 tumours, respectively. A higher prevalence of COX-2 overexpression in smaller size tumours was observed but this did not reach statistical significance. There was no relationship between COX-2 expression and lymph node status. Conclusions: This study did not support the generally held notion that COX-2 overexpression is linked to poor prognosis, rather supporting a role in tumorigenesis. Larger scale studies with outcome data and basic studies on cancer pathogenetic pathways will be required to cast further light on whether COX-2 inhibitors would have clinical utility in cancer prevention or blockage of cancer progression. In either setting, the pathological assessment for COX-2 overexpression in breast cancers would have an important role in the selection of cancer patients for personalized therapy with COX-2 inhibitors.

Impact of Bilateral Breast Cancer on Prognosis: Synchronous Versus Metachronous Tumors

  • Ibrahim, Noha Y.;Sroor, Mahmoud Y.;Darwish, Dalia O.
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1007-1010
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    • 2015
  • Background: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. Materials and Methods: Between 2005 and 2009 we identified 110 cases of bilateral breast cancer (BBC) ; 49 patients had synchronous (duration between the occurrence of carcinoma in both breasts was less than 12 months) and 61 had metachronous (duration was more than one year with no ipsilateral local recurrence). We compared the patient characteristics including age, menopausal status, clinical stage, tumor size, histological classification, lymph node status, and hormone receptor and Her-2 status. We also compared the treatment given and overall and disease free survival (DFS) of both groups. Results: Synchronous cases tend to present more aggressively than metachronous cases and age at first presentation adversely affects survival. The 5 year overall survival was 78.7% for metachronous and 60% for synchronous. Patients with positive hormonal status had better five year disease free survival in metachronous compared to synchronous cases, at 76% and 63%, respectively. Age at first presentation >45years had better DFS (65%) compared to those with age ${\leq}45$ years (52%) at 5 years follow up. Conclusions: Patients with synchronous breast cancer may have worse prognosis. Young age and hormone receptor negative were risk factors in our study. Close follow up and early detection of contralateral breast cancer is mandatory.