• Nuclear Medicine and Molecular Imaging
• /
• 제42권3호
• /
• pp.185-191
• /
• 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.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1997년도 춘계학술대회
• /
• pp.95-95
• /
• 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.

• Journal of Community Nutrition
• /
• 제4권1호
• /
• pp.3-11
• /
• 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.

• Archives of Pharmacal Research
• /
• 제27권5호
• /
• pp.524-530
• /
• 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..

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.9615-9619
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권4호
• /
• pp.1553-1558
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권3호
• /
• pp.1007-1010
• /
• 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.

• 대한예방의학회:학술대회논문집
• /
• 대한예방의학회 1999년도 제51차 추계 학술대회 연제집
• /
• pp.322-323
• /
• 1999

• 한국수의병리학회:학술대회논문집
• /
• 한국수의병리학회 2003년도 추계학술대회초록집
• /
• pp.40-40
• /
• 2003

The c-erbB2/neu oncogene (alias HER2, NEU) encoding a tyrosine kinase receptor protein, the overexpression of which correlates with a more rapid progression and a worse prognosis in human breast cancer [1]. Otherwise, this gene is still poorly investigated in veterinary oncology [2,3]. To gain insight into the patterns of c-erbB2/neu status in canine mammary tumor, we constructed one such mammary tumor tissue microarray (TMA) from 60 tumors from our lab. This enabled the amplification of c-erbB2/neu oncogene of all 60 tumors to be simultaneously analyzed by chromogenic in situ hybridization (CISH). The aim of this study was to evaluate status of c-erbB2/neu oncogene in canine mammary tumors and to correlate this status with the differentiation grade of neoplasm. (omitted)

• Investigative Magnetic Resonance Imaging
• /
• 제19권2호
• /
• pp.99-106
• /
• 2015

Purpose: To investigate factors influencing the evaluation of background parenchymal enhancement (BPE) at follow-up breast magnetic resonance imaging (MRI) after adjuvant endocrine therapy. Materials and Methods: One hundred twelve women with breast cancer and MRI of the contralateral unaffected breast before and after endocrine therapy were identified. Two readers in consensus performed blinded side-by-side comparison of BPE (minimal, mild, moderate, and marked) before and after therapy with categorical scales. Age, body mass index, menopausal status, treatment regimen (selective estrogen receptor modulator or aromatase inhibitor), chemotherapy, follow-up duration, BPE at baseline MRI, MRI field strength before and after therapy, and recurrence were analyzed for their influences on decreased BPE. Results: Younger age, premenopausal status, treatment with selective estrogen receptor modulator, MRI field strength, and moderate or marked baseline BPE were significantly associated with decreased BPE. In multivariate analysis, MRI field strength and baseline BPE showed a significant association. Conclusion: MRI field strength and baseline BPE before and after therapy .were associated with decreased BPE at post-therapy, follow-up MRI.