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Biomedical subjects

K O Park

Publications and source records attributed to K O Park.

At least 19 recordsLinked to original sources
PubMed2001

Apoptosis and bcl-2 expression as predictors of survival in radiation-treated non-small-cell lung cancer.

OBJECTIVES: We assessed the role of apoptosis and the expression of bcl-2, p53, and c-myc oncoproteins in pretreatment histologic specimens as a predictor of response to radiation therapy and survival in non-small-cell lung cancer (NSCLC) patients. METHODS: Pretreatment biopsy specimens of 68 patients with NSCLC (62 squamous cell carcinoma, 6 adenocarcinoma) were stained with hematoxylin and eosin. From 5 high-powered fields, the apoptotic index (AI) was calculated as the ratio of apoptotic tumor cells to the total number of tumor cells. Bcl-2, p53, and c-myc oncoprotein expression was detected by immunohistochemical staining. RESULTS: Twenty-nine cases showed partial or complete remission, whereas 39 showed no response. AI ranged from 0.2 to 12.0% (mean +/- SD; 4.3 +/- 2.6%, median 4.0%). There was no difference in AI between responders (4.0 +/- 2.3) and nonresponders (4.5 +/- 2.8, p > 0.05). However, in the responders, AI was correlated with the degree of change in tumor volume (r = 0.41, p < 0.05). In an analysis of 53 subjects who survived more than 1 month after the completion of radiation therapy, the patients with a higher AI (n = 27, MST = 22.8 m) survived longer than those with a lower AI (n = 26, MST = 9.2, log-rank, p = 0.03). Patients expressing bcl-2 had poorer survival (n = 22, MST = 6.0 m) than patients without bcl-2 (n = 31, 22.8 m, p < 0.003). According to multivariate analysis, three variables, bcl-2 expression, AI, and response to radiation, were independent prognostic factors for survival. CONCLUSION: A low level of spontaneous apoptosis and expression of apoptosis blocking bcl-2 protein in pretreatment histology predict a poor prognosis for radiation-treated NSCLC patients.

Adenocarcinoma↗
PubMed2001

The relationship between microvessel count and the expression of vascular endothelial growth factor, p53, and K-ras in non-small cell lung cancer.

Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, and vascular endothelial growth factor (VEGF) in 61 surgically resected non-small cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significantly higher than that of tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200 field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras-positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ according to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF expression, leading to angiogenesis and ultimately lymph node metastasis. Correlations between variables in close approximation and the lack of prognostic significance of individual molecular alterations suggest that tumorigenesis and metastasis are multifactorial processes.

Adult↗
PubMed2000

Different cutoff values of Cyfra 21-1 for cavitary and noncavitary lung cancers.

STUDY OBJECTIVES: Cell lysis and tumor necrosis release cytokeratin, a tumor marker of lung cancer, into the serum. The serum cytokeratin level can also be elevated in benign cavitary lung diseases. The purpose of this study was to evaluate whether Cyfra 21-1 can differentiate malignant lung diseases from benign diseases with cavitary lesions. DESIGN: This study is a retrospective review of the case records of patients with lung lesions seen during a 4-year period from January 1993 to May 1996. SETTING AND PATIENTS: Serum Cyfra 21-1 levels were measured in 306 patients with lung cancer (n = 143) or benign lung disease (n = 163). The patients were grouped according to radiologic evidence of cavitary lung lesions. Lung cancer included both non-small cell (n = 123) and small cell (n = 20) lung cancers, and the benign diseases include tuberculosis (n = 87), abscess (n = 26), pneumonia (n = 4), and others (n = 46). MEASUREMENTS AND RESULTS: Although Cyfra 21-1 clearly differentiated cavitary lung cancer (15.0, 9.1-29.8 ng/ml, median and interquartile range, n = 39) from benign cavitary disease (P < 0.001), and noncavitary lung cancer from benign noncavitary disease (1.7, 0.9-2.6 ng/ml, n = 108, P < 0.001), it could not differentiate noncavitary lung cancer (5.0, 2.1-12.4 ng/ml, n = 104) from benign cavitary diseases (3.3, 1.4-8.3 ng/ml, n = 55, P = 0.45). CONCLUSIONS: Serum Cyfra 21-1 is a useful tumor marker for differentiating benign from malignant lung diseases. However, different cutoff values are needed, depending on the presence of cavitary lesions. We recommend cutoff values of 30 ng/ml for cavitary lung diseases and 6 ng/ml for noncavitary lung diseases. If there are no radiologic data, a cutoff value of 15 ng/ml is recommended.

Adult↗
PubMed2000

Comparison of Tc-99m sestamibi, serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy in small cell lung cancer.

Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are tumor markers of small cell lung cancer (SCLC) which were reported to predict outcome of patients with SCLC. We previously reported that dipyridamole-modulated Tc-99m sestamibi (dipyridamole-MIBI) single photon emission computed tomography (SPECT) could predict the response to chemotherapy in SCLC patients. The purpose of this study was to compare dipyridamole-MIBI and pretreatment serum levels of NSE and LDH for the prediction of response to chemotherapy in SCLC. Twenty-eight SCLC patients underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at lease two cycles). Serum levels of NSE and LDH were also measured at the same day of the imaging. Tomographic images before and after 0.84 mg/kg dipyridamole infusion were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete (CR), partial response (PR), no change (NC), and progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. Among the 28 patients, 15 were responders (2 CR, 13 PR) and 13 were nonresponders (11 NC, 2 PD). The change of tumor-to-normal lung ratio (T:NL) after infusion of dipyridamole was significantly higher in responders as compared with nonresponders (0.38 +/- 0.64 vs. -0.38 +/- 0.50, respectively, p = 0.002). However, pretreatment serum NSE and LDH levels did not correlate with the response to chemotherapy. Increase of T:NL after dipyridamole infusion was a strong negative predictor of chemotherapeutic response in SCLC patients, while NSE and LDH could not predict it.

Aged↗
PubMed2000

Vascular endothelial growth factor in malignant and tuberculous pleural effusions.

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.

Endothelial Growth Factors↗
PubMed2000

The role of E-cadherin expression in non-small cell lung cancer.

The purpose of this study is to evaluate the clinical significance of E-cadherin expression in lung cancer. E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1). Strongly positive (++) E-cadherin tumors were classified as a type of preserved E-cadherin expression (Pr type), while the others (+, - tumors) were classified as a type of reduced E-cadherin expression (Rd type). The frequency of Pr type in squamous cell carcinomas (59.0%) was higher than Rd type. However, in adenocarcinomas, the frequency of Rd type was higher than Pr type. E-cadherin expression pattern was significantly correlated with differentiated state (Pearson correlation coefficient 0.394, p<0.001). E-cadherin expression of well-differentiated tumors was more frequently preserved than that of poorly differentiated tumors (60.0% vs. 25.9%). With regard to the correlation between E-cadherin expression and stages of lymph node metastasis in non-small cell lung cancers, the percentage of tumors with Pr type E-cadherin expression declined from 66.3% (< or = N1) to 38.6% (> or = N2), indicating that loss of E-cadherin expression is responsible for acquisition of invasive potential of lung cancer as well as the possible role of E-cadherin in the histological differentiation of lung cancer.

Adult↗
PubMed2000

Pleural empyema due to Salmonella: a case report.

Pleuropulmonary involvement of salmonella infection is very rare and only two cases of salmonella empyema have been reported in Korea. We report the case of a 70-year-old female diabetic patient who presented with right flank pain and right lower chest pain. The chest radiographs revealed fibrostreaky and hazy density at right lower lung field and blunting of right costophrenic angle. Thoracentesis revealed turbid yellowish fluid. Salmonella group B was identified from the cultures of blood and pleural fluid. After antimicrobial therapy and repeated therapeutic thoracentesis, the patient was improved.

Aged↗
PubMed2000

A case of Cushing's syndrome in ACTH-secreting mediastinal paraganglioma.

Paragangliomas are unusual neuroendocrine cell tumors arising from paraganglia, of which ACTH-secreting cases in the mediastinum are extremely rare. A 51-year-old woman was admitted for generalized edema and weakness which began 5 months ago. Chest X-ray and CT scan revealed a tumor mass in the anterior mediastinum. The plasma cortisol and ACTH levels were very high. Other sources secreting ACTH, except mediastinal mass, were not found. Surgical excision of mediastinal mass and left supraclavicular lymph node was performed. The postoperative microscopic finding and immunohistochemical staining revealed organoid tumor cell nests (zellballen) and S-100 protein positive sustentacular cells which are characteristics of paraganglioma. This was thus a case of Cushing's syndrome resulting from ectopic ACTH production in anterior mediastinal paraganglioma.

Adrenocorticotropic Hormone↗
PubMed1999

Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects.

BACKGROUND AND OBJECTIVE: The role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)-5 in induced sputum from asthmatics. METHODS: Hypertonic saline-induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti-asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospinned for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL-5 by a sandwich ELISA. RESULTS: Asthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 +/- 125.3 vs 557.2 +/- 101.5 micromol/L, P < 0.01), higher percentage of eosinophils (25.6 +/- 4.6 vs 1.7 +/- 0.2%, P < 0.01), and higher levels of ECP (1117.8 +/- 213.9 vs 154.6 +/- 47.4 microg/L, P < 0.01) in the induced sputum. IL-5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n = 18) had higher level of NO metabolites (1143.8 +/- 156.3 vs 575.5 +/- 89.5 micromol/L, P < 0. 01), higher levels of ECP and IL-5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n = 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL-5 were reduced following treatment with anti-asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r = 0. 34, P < 0.05; r = 0.28, P < 0.05). Negative correlations were noted between FEV1, FEV1/FVC and proportion of eosinophils, ECP, or IL-5 levels. CONCLUSION: These findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.

Adolescent↗
PubMed1999

Dipyridamole modulated Tc-99m sestamibi lung SPECT in small cell lung cancer.

PURPOSE: In this study, the authors wanted to determine whether dipyridamole-modulated MIBI (dipyridamole-MIBI) could enhance the prediction of the response to chemotherapy in patients with small cell lung cancer. METHODS: Twenty-seven patients with biopsy-proved small cell lung cancer (25 men, 2 women; mean age, 61 +/- 7 years) underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at least two cycles). Tomographic images before and after dipyridamole (0.84 mg/kg) were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete response (CR), partial (PR), no change (NC), or progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. RESULTS: Among the 27 patients, 22 were responders (3 CR, 19 PR) and 5 were nonresponders (3 NC, 2 PD). The tumor-to-normal lung ratio (T:NL) of responders was significantly higher than that of nonresponders. The diagnostic accuracy of the T:NL ratio to differentiate responders and nonresponders was 33.3%, with a cutoff value of 2.5, which was significantly improved to 77.8% when an increased T:NL ratio after dipyridamole was assigned to a nonresponder. Furthermore, all patients with CR showed diminished T:NL ratios after dipyridamole, and all patients with NR showed an increased T:NL ratio after dipyridamole. CONCLUSION: Dipyridamole-MIBI SPECT could enhance the prediction of response to chemotherapy in patients with small cell lung cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients.

In patients with non-small cell lung cancer (NSCLC), tumor expression of P21-Ras, HER2, P53, and Bcl-2 has been reported as independent predictors of prognosis. However, the prognostic information carried by these proteins has usually been determined separately, and their potential interaction has not been taken into account. We conducted immunostaining for P21-Ras, HER2, P53 and Bcl-2 on 238 cases of NSCLC in a Korean population with 203 squamous cell carcinomas, and 35 adenocarcinomas. P21-Ras, HER2, P53 or Bcl-2 was expressed at high levels in 54.6, 42.0, 18.1 and 71.8% of the NSCLC studied, respectively. A total of 59 tumors (24.8%) expressed only one protein, while 70 (29.4%) expressed two, 59 (24.8) expressed three, and 17 tumors (7.1%) expressed all four proteins. Univariate analysis testing the association of marker expression with survival found Bcl-2 expression to be significantly associated with a poor prognosis, as well as the co-expression of Bcl-2 + HER2, Bcl-2 + HER2 + P53, and Bcl-2 + HER2 + P53 + P21-ras with an increasing hazard ratio. By multivariate analysis controlling for age, tumor stage and tumor type, only the combination of Bcl-2 + HER2 expression was an independent marker of poor prognosis (hazard ratio = 1.91, P = 0.003). Thus, a prospective analysis of the co-expression of Bcl-2 + HER2 in NSCLC patients may identify patients with a poor prognosis who may benefit from more aggressive therapy.

Adenocarcinoma↗
PubMed1998

Technetium-99m-MIBI uptake in small cell lung cancer.

UNLABELLED: Patients with small cell lung cancer (SCLC) often fail to respond to chemotherapy due to multidrug resistance (MDR). Technetium-99m-MIBI was reported to be a suitable transport substrate of P-glycoprotein, which is a cytoplasmic membrane protein encoded by the MDR gene. The purpose of this study was to evaluate whether or not the degree of MIBI uptake in SCLC or its retention on delayed imaging correlated with response to chemotherapy. METHODS: Twenty-five patients (19 men, 6 women; mean age 59 +/- 10 yr) with biopsy-proven SCLC had MIBI SPECT 3-7 days before starting chemotherapy. Imaging was acquired 1 and 4 hr after injection of 740 MBq MIBI using a single-head rotating gamma camera. Tumor-to-normal lung uptake ratio (T/NL) was measured. Percent retention (%R) was measured as: %R = 100 x (T/NL at 4 hr)/(T/NL at 1 hr). All patients received VAP chemotherapy (VP-16 100 mg/m2, adriamycin 40 mg/m2, cisplatin 25 mg/m2) every 4 wk for at least three times. Response to chemotherapy was grouped as complete remission, partial remission and no remission according to the change of tumor size on chest radiograph and CT images. Differences in T/NL and %R among the three groups were analyzed using ANOVA. RESULTS: T/NL of patients with complete remission (n = 7) and partial remission (n = 10) were significantly higher than that of no remission (n = 8) in 1 hr and 4 hr. T/NL at 1 hr in three groups were 2.75 +/- 0.78, 2.35 +/- 0.31 and 1.65 +/- 0.36, respectively. T/NL at 4 hr in three groups was 2.61 +/- 0.94, 2.48 +/- 0.50 and 1.66 +/- 0.42, respectively. However, %R was not different among three groups. Percent retention in three groups was 109.40 +/- 22.10, 96.71 +/- 14.25 and 103.59 +/- 28.43, respectively. CONCLUSION: SCLC with a higher MIBI uptake was more likely to respond to chemotherapy than that with a lower uptake. However, there was a considerable overlap of MIBI uptake among subjects. No significant correlation between the MIBI retention between 1 hr and 4 hr, and the response to chemotherapy was noted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Combining ADA, protein and IFN-gamma best allows discrimination between tuberculous and malignant pleural effusion.

BACKGROUND: The purpose of this study is to assess the usefulness of various enzymes, cytokines and biochemical studies of pleural fluid for the differential diagnosis of tuberculosis from malignant pleural effusions, and to clarify the role of combining diagnostic tests. METHODS: The study group included 39 cases with tuberculous effusions and 31 cases with malignant effusions, whose diagnoses were confirmed by pleural biopsy, cytology or microbiological methods. We compared pleural fluid levels of ADA, TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8, pH, protein, glucose, cholesterol, triglyceride, amylase and lactic dehydrogenase between tuberculous and malignant effusions. Using stepwise logistic regression analysis, we evaluated the benefit of combining various parameters. Receiver operating characteristic(ROC) curves of ADA, cytokines and equations generated from regression analyses were plotted and compared with the area under curve(AUC). Cut-off values showing the best diagnostic accuracy were selected and compared. RESULTS: Compared to malignant effusion, tuberculous effusion showed significantly higher levels of ADA, IFN-gamma, TNF-alpha and IL-2. There was a good correlation between IFN-gamma and TNF-alpha. By stepwise logistic regression analysis, IFN-gamma, protein and ADA were independent variables predicting tuberculous from malignant effusions. The diagnostic accuracy and AUC of regression equation was greater than any other single parameters. CONCLUSION: For the differential diagnosis of tuberculosis and malignant pleural effusions, combining ADA, protein and IFN-gamma best allows discrimination.

Adenosine Deaminase↗
PubMed1996

A comparison of serum CYFRA 21-1 and SCC Ag in the diagnosis of squamous cell lung carcinoma.

To evaluate the usefulness of CYFRA 21-1 and SCC Ag in the diagnosis of squamous cell carcinoma (SQC) of the lung, we tested sera from 124 patients with lung cancers (squamous cell ca 72, adenoca 22, large cell ca 4, small cell ca 18 and undetermined 8) and 78 patients with inflammatory lung diseases (bronchitis 24, bronchiectasis 29, tuberculosis 19 and others 6) using immunoradiometric assay kit for cytokeratin fragment 19 (CYFRA 21-1) and radioimmunoassay kit for SCC Ag. The serum CYFRA 21-1 and SCC Ag were significantly higher in lung cancer patients compared with control subjects. However, the significant difference was restricted only to SQC. In patients with SQC, CYFRA 21-1 and SCC Ag showed significantly higher levels according to the advanced anatomic stages (stage I-IIIa vs. stage IIIb, IV, p < 0.05). There was a good correlation between CYFRA 21-1 and SCC Ag (r = 0.41, p < 0.001). Receiver operating characteristic (ROC) curves were generated from results of both tumor markers and areas under the curves (AUC) were calculated. AUC of CYFRA 21-1 (0.93) were significantly larger than that of SCC Ag (0.77) for the diagnosis of SQC (p < 0.05). Therefore, we conclude that CYFRA 21-1 is superior to SCC Ag in the diagnosis of squamous cell carcinoma of the lung.

Aged↗
PubMed1996

Acute lung injury after phosgene inhalation.

Phosgene (COCl2) is a colorless oxidant gas which is heavier than air and the lethal exposure dose (LC50) in humans is 500 ppm/min. This gas was originally manufactured as an agent for chemical warfare during World War I and there had been a great deal of studies on phosgene poisoning during the early years of industrial use. It is still widely used in the synthesis of chemicals and plastics. In the modern era, however, phosgene poisoning is relatively uncommon except in accidental exposures. In Korea, there has been no report about lung injury from phosgene inhalation. We present a clinical experience with six patients accidentally exposed to phosgene.

Accidents, Occupational↗
PubMed1996

DNA ploidy and proliferative activity in bcl-2 expressed non-small cell lung cancer.

OBJECTIVES: The expressions of bcl-2 have been reported recently in non-small cell lung carcinoma (NSCLC*). As oncogensis is believed to involve a number of genetic alterations, there can be differences in DNA ploidy or proliferative activity even in bcl-2 positive cases according to the superimposed genetic events. SUBJECTS AND METHODS: On the assumption that we might further discern the biologic behavior of bcl-2 positive NSCLC according to the status of DNA ploidy and proliferative activity, we conducted a study for bcl-2 expression with immunohistochemical staining and DNA analysis on 52 surgical specimens of NSCLC. RESULTS: The bcl-2 was positive in 52% (27/52) of specimens, According to the status of bcl-2 expression, there were no significant differences in tumor stages, performance status score and survival time. Among bcl-2 positive NSCLC, aneuploidy and high proliferative activity were noted in 40% and 44%, respectively. In cases with squamous cell carcinoma (SQC**), the proportion of aneuploidy was significantly higher in bcl-2 positive group compared to bcl-2 negative group (p < 0.01), which could not be explained with the sole effect of bcl-2. In bcl-2 positive NSCLC, there was no significant survival difference by the status of DNA analysis results. With a Coxproportional hazard model, only T stage was an independent prognostic factor. CONCLUSION: In bcl-2 expressed NSCLC, proliferative activity and DNA ploidy were not homogeneous, suggesting other genetic alterations. This may explain our results which showed no differences in survival according to the status of the bcl-2 expression.

Adult↗