Analysis of PIK3CA Mutation Concordance and Frequency in Primary and Different Distant Metastatic Sites in Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. @*Materials and Methods@#Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. @*Results@#After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. @*Conclusion@#The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.

TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). @*Materials and Methods@#Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. @*Results@#TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines @*Conclusion@#Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Molecular engineering of antibodies for site-specific conjugation to lipid polydopamine hybrid nanoparticles

Conjugation of antibodies to nanoparticles allows specific cancer targeting, but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody. Here, a molecular engineering technique was used for site-specific conjugation of antibodies to nanoparticles. We designed an anti-claudin 3 (CLDN3) antibody containing a single cysteine residue, h4G3cys, then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles (LPNs). Because of their negatively charged lipid coating, LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4G3cys. The activity of h4G3cys was tested by measuring the binding of h4G3cys-conjugated LPNs (C-LPNs) to CLDN3-positive tumor cells and assessing its subsequent photothermal effects. C-LPNsspecifically recognized CLDN3-overexpressing T47D breast cancer cells but not CLDN3-negative Hs578T breast cancer cells. High binding of C-LPNs to CLDN3-overexpressing T47D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy. Consistent with this, intravenous injection of C-LPNsin a T47D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases. Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.

A case of Hyper-IgE syndrome with a mutation of the STAT3 gene / 소아과

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disease which is characterized by high serum IgE levels, eczema, and recurrent infections. Herein we present the case of a patient with HIES associated with STAT3 gene (stat3) mutation. A 16 year-old girl was admitted to our hospital due to hemoptysis caused by pneumonia with bronchiectasis. She had a history of recurrent skin and respiratory tract infections, such as pneumonia caused by MRSA (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa. On physical examination, a broad round shaped nose, oral thrush, and chronic eczematous skin rash over her whole body were found. Laboratory data showed an elevated eosinophil count (750/microliter) and total IgE level (5,001 U/mL). The patient's National Institutes of Health (NIH) score for HIES was 44. Direct sequencing of the STAT3 gene revealed that the patient was heterozygous for a missense mutation in the DNA binding domain of the STAT3 protein (c.1144C>T, p. Arg382Trp). HIES should be suspected in patients with recurrent infections and can be confirmed by clinical scoring and genetic analysis.

Immature thymocyte antigen, JL1, as a possible immunodiagnostic and immunotherapeutic target for leukemia

The identification of tumor-specific antigens has represented a critical milestone in cancer diagnosis and therapy. Clinical research in this area for leukemia has also been driven over the past few decades by the hope that surface antigens with restricted tissue expression would be identified. Disappointingly, only a small number of the leukemic antigens identified to date, meet sufficient criteria to be considered viable immunophenotypic markers. In this paper, we nominate anti-JL1 monoclonal antibody as an immunodiagnostic and immunotherapeutic candidate for leukemia. The JL1 molecule appears to be a novel cell surface antigen, which is strictly confined to a subpopulation of limited stages during the hematopoietic differentiation process. Despite the restricted distribution of the JL1 antigen in normal tissues and cells, anti-JL1 monoclonal antibody specifically recognizes various types of leukemia, irrespective of immunophenotypes. On the basis of these findings, we propose JL1 antigen as a tumor-specific marker, which shows promise as a candidate molecule for diagnosis and immunotherapy in leukemia, and one that spares normal bone marrow stem cells.

High CD99 expression in memory T and B cells in reactive lymph nodes

We investigated the expression of CD99 in 35 hyperplastic perigastric lymph nodes, which were resected for gastric carcinoma or chronic peptic ulcer. Essentially, all lymphocytes in lymph nodes expressed CD99, but there were two populations with respect to the intensity of CD99 expression--CD99high and CD99low cells. We showed CD99high cells were distributed in paracortical and medullary cords by immunohistochemical study while germinal center cells were CD99low. Using three-color flow cytometric analysis with CD3, CD4, CD8, CD19, CD23, CD45RA, CD45RO, CD69, CD138, IgM, IgD, and IgG, most of CD99high cells were shown to be activated/memory T cells. CD4+CD45RO+ T cells were the subset revealing the highest intensity of CD99 expression while CD4+CD45RA+ T cells were CD99low. Among B cells, IgG+ B cells revealed a higher level of CD99 molecules than IgM+ B cells. These results suggest that CD99 is one of activation-related molecules which are upregulated in recently activated lymphocytes.

Relation of Serum Eosinophilic Cationic Protein, Eosinophil and Neutrophil Count to Pulmonary Function and Smoking History / 대한내과학회지

OBJECTIVES: A prospective study was performed to find out the correlation between neutrophil, eosinophil and eosinophilic cationic protein (ECP)-the granular protein in eosinophil- and smoking history and pulmonary function change, METHODS: In this study there were seventy smokers and seventy lifetime nonsmokers. None of them had the history of atopy, or the evidence of parasitic infestation. Smoking history, spirometric pulmonary function test and blood samples for CBC, serum ECP were analyzed. RESULTS: 1) Eosinophil and neutophil count was elevated in the smokers compared with the nonsmokers. 2) Serum ECP was elevated in smokers and the magnitude of this increase was greater than that of eosinophil count. 3) In the smokers, there was a direct proportional correlation between serum ECP and FEV1, but inverse proportional correlation between neutophil count and FEV. 4) In the smokers, neutrophil count was elevated regardless of FEV value. 5) The level of serum ECP well correlated with the daily tobacco consumption but not with the duration of smoking or pack-year consumption. CONCLUSION: Incresed neutrophil count, decreased eosinophil count and decreased serum ECP level could be useful in the understanding of pathophysiology of lung parenchymal destruction in smokers.

The effect of Postural Changes on Pleural Fluid Constituents / 결핵

BACKGROUND: Measurement of pleural fluid constituents are of value in the diagnosis of pleural effusions and in the seperation of exudates from transudates. The position of the patient (sitting or lying) prior to thoracentesis may result in difference in the measurement of these constituents. The purpose of this study is to determine whether postural differences in pleural fluid constituents exist, and if so, whether they are of any clinical significance. METHOD: 41 patients with pleural effusions on chest roentgenography were prospectively studied. The fluid cell counts, partial gas tension, and concentrations of chemical constituents were compared in the supine and upright positions. RESULTS: 1) A total of 10 patients were found to have an transudative effusion. In the transudates there was no significant difference in pleural fluid constituents according to posture change. 2) A total of 31 patients were found to have an exudative effusion. Statistically significant postural changes were noted in pH, WBC counts, protein, and LDH concentrations in the exudates. It may be due to postural sedimentary effect in the pleural space. 3) The PC02 measurements and glucose concentration were not affected by changes in position in exudates or transudates. CONCLUSION: Postural sedimentary effect occurs in the pleural space with reference to the measurement of certain pleural fluid constituents when an inflammatory process is present. Therefore it is recommended that thoracentesis after 30 minutes in the sitting position should be performed.

A case of mediastinal cystic lymphangioma / 결핵

No abstract available.

Diagnostic significance of cholesterol in pleural effusion / 결핵

No abstract available.

A Comparative Study of Echocardiographic Dilated Cardiomyopathy According to Its Etiologic Factors

The characteristics of echocardiographic dilated cardiomyopathy according to its etiologic factors were studied from June, 1984 to September, 1986 in Pusan national University Hosptial. The cases included in the study were 144 patients, 90 cases of male and 54 cases of female respectively ranging the age from 17 years old to 79 years old. Patients with valvular heart disease were excluded in this study. The results were as follows: 1) Primary dilated cardiomyopathy was 40.3%, and secondary dilated cardiomyopathy was 59.7% of the study group. In secondary dilated cardiomyopathy, its etiologic factors were hypertension 17.4%, ischemic heart disease 27.8%, thyrotoxicosis 5.6%, chronic renal failure 4.8%, pregnancy 3.4% and alcohol drinking 0.7%. 2) Atrial fibrillation was noted in 32.6% of primary, 36.0% of hypertensive, 30.0% of ischemic and 62.5% of toxic cardiomyopathy. Conduction disturbance was noted in 57.1% of uremic cardiomopathy, it was far more frequent comparing with other cases of cardiomyopathy ranging 20-30%. 3) The frequency of end-diastolic internal dimension of left ventricle over 6.0cm was 58.6% in primary, 68.0% in hypertensive, 75.0% in ischemic, 71.4% in uremic and 40.0% in postpartum cardiomyopathy. 4) The frequency of ejection fraction of left ventricle below 40% was 17.2% in primary, 8.0% in hypertensive, and 28.2% in ischemic cardiomyopathy. 5) The paradoxical motion of anteroseptal wall of left ventricle was observed in 6.9% of primary, 4.0% of hypertensive, and 17.5% of ischemic cardiomyopathy. The ratio of anteroseptal wall motion to posterior wall motion below 0.4 was 15.6% in primary, 20.0% in hypertensive, and 25.0% in ischemic cardiomyopathy. 6) The frequency and grade of mitral regurgitation became increased with the dilatation of left ventricle. 7) The follow-up of cardiothoracic ratio was helpful significantly in the prediction of prognosis.

A Clinical Trial on Antihypertensive Effect of Pindolol(Visken(R))

The antihypertensive effect and side reaction of pindolol were studied in 48 cases of essential hypertension 5mg to 15mg once regiment for average period of 6 weeks. 1) Average reduction of 25.11mmHg in systolic and 16.36mmHg in diastolic pressure were observed and their percentile reduction was 15.20% and 14.79%, respectively. The overall effect rate was 83.21%. The blood pressure was lowered significantly since 1 week of both in systolic and diastolic pressure with the daily of 10-15mg. 2) There was no significant change in heart rate before and after treatment. 3) No specific side reaction was observed except 1 cases in which discontinued the medication because of severe headache and fatigability on 2nd day of medication.

A Clinical Trial on Antihypertensive Effect of Nicardipine Hydrochloride

The antihypertensive effect and side reactions of perdipine was studied in 22 cases of essential hypertension using 20mg 3 times daily regimen for average period of 5 weeks. 1) Average reduction of 20mmHg in systolic and 17mmhg in diastolic pressure was observed and percentile reduction was 11.90% and 14.92%, respectively. The overall effect rate was 81.82%. The blood pressure lowered significantly after 2 weeks of treatment both in systolic and diastolic pressure. 2) There was no significant change in heart rates before and after treatment. 3) No specific side reaction was observed except 1 case in which discontinued the medication because of severe headache and fatigability on the 1st day of medication.

Assessment of Aortic Regurgitation by Real-time Two-dimensional Doppler Flow Mapping System

In the real-time two-dimensional Doppler flow mapping(2DD) system, Doppler signals are processed using auto-correlation technique, so that the direction, velocity and turbulence of the intracardiac blood flow are displayed by coloration on the B mode image of the heart in real time. Aortic regurgitant flow is imaged as a mosaic jet spurting out from the aortic valve orifice to cardiac chamber. Dynamic features in the direction and extent of regurgitant flow and the site of regurgitation on the aortic valve orifice are readily obtained. Feasibility of the 2DD system in the assesment of aortic regurgitation was examined in 30 cases documented by angiography. In 30 cases, there were 20 cases with aortic regurgitation(AR) aged 16 to 57 years(mean 34) and 10 cases without AR aged 17 to 39 years(mean 30). The underlying disorders of AR were rheumatic in 15 cases, bicuspid aortic valve in 1, ventricular septal defect in 1, aortitis in 1, Marfan's syndrome in 1 and unknown in 1. The results are as follows : 1) In 19 out of 20 cases with AR the 2DD showed regurgitant jet spurting out from valve orifice(sensitivity=95%). One case missed by the 2DD had 1+AR. None of the 10 cases who had no AR manifested the evidence of AR on the 2DD(specificity=100%). 2) There was an excellent positive correlation between the maximal jet length of regurgitant flow on the 2DD and angiographic severity of regurgitation(r=0.998, p or = 3+) AR. 5) In all 8 cases with fluttering of anterior mitral leaflet and 8 out of 9 cases with fluttering of interventricular septum, a regurgitant jet impinged on them. The results of this investigation indicate that the 2DD system is a very useful and unique noninvasive technique in the detection, estimation of severity and spatial orientation of AR.

A Clinical Trial on Antihypertensive Effect of Tripamide(Normonal(R))

Antihypertensive effect and side effect of Tripamide(Normonal(R)) was studied in 22 cases of essential hypertension using 15mg once daily regimen for average period of 9 weeks. 1) Antihypertensive effect Average reduction of 25mmHg in systolic and 19mmHg in systolic and 19 mmHg in diastolic pressure was observed and reduction rate was 15.7% and 17.6% respectively. The overall effect rate was 86%. The blood pressure lowered significantly in 1 week of treatment both in systolic and diastolic pressure and the extent of fall in systolic pressure approached near the level of maximum reduction in 2 weeks of administration and that of diastolic after 5 weeks of treatment. 2) Laboratory tests and side effect There was no significant changes in individual and mean value of Na, K, Cl, BUN, creatinine, uric acid, fasting blood sugar, cholesterol, GOT, GPT studied before and after treatment except one case showing elevation of uric acid. No significant side effect was observed during trial except of 2 cases of transient diuretic effect.

The Relationship of Mitral Valve Area Measured by 2-Dimensional Echocardiography with the M-Mode Measurements in Mitral Valvular Stenosis

Mitral valvular orifice area is important for the evaluation of prognosis and treatment of patients with mitral valvular stenosis. Until recently, Gorlin's formula using cardiac catheterization has been utilized in the measurement of mitral valve area, but it is invasive and impractical to examine repeatedly. Recently 2-Dimensional echocardiography appeared to be a practical and useful substitute in measurement of valve area and also it is economical and has no risk to patients. In 31 patients with mitral valvular stenosis examined at the echocardiography room of Busan national University Hospital from March 1982 to March 1983, we measured the mitral valve area with 2-Dimensional echocardiography and evaluated its relationship with the left ventricular functions measured on M-mode echocardiogram. Among many parameters on M-mode measurements EF slope, excursion amplitude and the ratio of left atrial dimension to aortic root dimension were rather helpful for the assessment of severity of mitral valvular stenosis than other parameters. And each relationship with the valve area showed correlation coefficient of 0.60, 0.05 and -0.58, respectively.