1.Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells
So Jin SIM ; Jeong-Hoon JANG ; Joon-Seok CHOI ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2024;32(5):568-576
Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.
2.Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells
So Jin SIM ; Jeong-Hoon JANG ; Joon-Seok CHOI ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2024;32(5):568-576
Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.
3.Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells
So Jin SIM ; Jeong-Hoon JANG ; Joon-Seok CHOI ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2024;32(5):568-576
Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.
4.Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells
So Jin SIM ; Jeong-Hoon JANG ; Joon-Seok CHOI ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2024;32(5):568-576
Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.
5.Anaphylaxis to Polyethylene Glycol (Colyte®) in a Patient with Diverticulitis.
So Hee LEE ; Sun Hyuk HWANG ; Jin Soo PARK ; Hae Sim PARK ; Yoo Seob SHIN
Journal of Korean Medical Science 2016;31(10):1662-1663
Polyethylene glycols (PEGs) are believed to be chemically inert agents, but larger PEG polymers could have immunogenicity. A 39-year-old man was referred to emergency room for loss of consciousness and dyspnea after taking of PEG-3350 (Colyte®). In laboratory findings, the initial serum tryptase level was increased to 91.9 mg/L (normal range: 0.00-11.40 mg/L) without any other laboratory abnormalities. The intradermal test with 10 mg/mL Colyte® showed a 5 × 5 mm wheal, but basophil activation and histamine releasability tests were negative. PEG-3350 is widely used as an osmotic laxative due to its lack of absorption from the gastrointestinal tract. However, the loss of mucosal integrity at gastrointestinal membrane such as diverticulitis may be a predisposing factor for anaphylaxis to Colyte®. We report a case of anaphylaxis induced by the ingestion of PEG-3350 in a patient with diverticulitis which might be a risk factor of anaphylaxis.
Absorption
;
Adult
;
Anaphylaxis*
;
Basophils
;
Causality
;
Diverticulitis*
;
Dyspnea
;
Eating
;
Emergency Service, Hospital
;
Gastrointestinal Tract
;
Histamine
;
Humans
;
Intradermal Tests
;
Membranes
;
Polyethylene Glycols*
;
Polyethylene*
;
Polymers
;
Risk Factors
;
Tryptases
;
Unconsciousness
6.Hemolytic-Uremic Syndrome Associated with Bloody Diarrhea.
Jung Sim KIM ; Eun Jung PARK ; So Hee CHUNG ; See Hwan KO ; Mee Ryung UHM ; Moon Su PARK ; Heung Jea LEE ; Dong Kyu JIN
Journal of the Korean Society of Pediatric Nephrology 1997;1(2):170-175
The authors analysed 2,653 cases of transthoracic fine needle aspiration cytology of the lung to evaluate the diagnostic accuracy and its limitation. A comparison was made between the original cytologic and the final histologic diagnoses on 1,149 cases from 1,074 patients. A diagnosis of malignancy was established in 38.3% benign in 48.1%, atypical lesion in 2.3%, and inadequate one in 11.9% of the cases. Statistical data on cytologic diagnoses were as follows; specificity 98.9%: sensitivity of procedure, 76.8%: sensitivity of diagnosis, 95.5%: false positive 5 cases: false negative 18 cases: predictive value for malignancy, 98.8%: predictive value for benign lesion, 79.5%: overall diagnostic efficiency, 87.5%: typing accuracy in malignant tumor, 80%.
Biopsy, Fine-Needle
;
Diagnosis
;
Diarrhea*
;
Hemolytic-Uremic Syndrome*
;
Humans
;
Lung
;
Sensitivity and Specificity
7.A Case of Trigemjinal Neurinoma in Puberty.
Byung Kyu CHO ; Gook Ki KIM ; Myong Sun MOON ; Jin CHAE ; Kil So CHOI ; Bo Sung SIM
Journal of Korean Neurosurgical Society 1974;3(1):129-132
Trigeminal neurinoma is a rare condition arising from the gasserian or trigeminal nerve root. It comprises 0.2% of all brain tumors, and usually affects middle life, but about 10% of it appears in adolescents. Middle fossa syndrome, symptoms and signs of cerebellopontine angle tumor and mixture of these may be developed through the extension of the tumor. Symptoms and signs of cerebellar and midbrain compression may also be elicited in some stage of the tumor. Erosion of the Anteromedial portion of the petrous apex and defect of the flow of the middle fossa contribute to the diagnosis. Air studies and cerebral antiography have been used, and recently pantopaque basal cisternography has been introduced. The route of operation depends upon the main localization of the tumor, but transtemporal approach with tentorial section is widely used for dumbbell-shaped tumor. A case of cerebellopontine angle tumor which had been postoperatively proved to be a trigeminal neurinoma is reported.
Adolescent
;
Brain Neoplasms
;
Diagnosis
;
Humans
;
Iophendylate
;
Mesencephalon
;
Neurilemmoma*
;
Neuroma, Acoustic
;
Puberty*
;
Trigeminal Nerve
8.A Case of Trigemjinal Neurinoma in Puberty.
Byung Kyu CHO ; Gook Ki KIM ; Myong Sun MOON ; Jin CHAE ; Kil So CHOI ; Bo Sung SIM
Journal of Korean Neurosurgical Society 1974;3(1):129-132
Trigeminal neurinoma is a rare condition arising from the gasserian or trigeminal nerve root. It comprises 0.2% of all brain tumors, and usually affects middle life, but about 10% of it appears in adolescents. Middle fossa syndrome, symptoms and signs of cerebellopontine angle tumor and mixture of these may be developed through the extension of the tumor. Symptoms and signs of cerebellar and midbrain compression may also be elicited in some stage of the tumor. Erosion of the Anteromedial portion of the petrous apex and defect of the flow of the middle fossa contribute to the diagnosis. Air studies and cerebral antiography have been used, and recently pantopaque basal cisternography has been introduced. The route of operation depends upon the main localization of the tumor, but transtemporal approach with tentorial section is widely used for dumbbell-shaped tumor. A case of cerebellopontine angle tumor which had been postoperatively proved to be a trigeminal neurinoma is reported.
Adolescent
;
Brain Neoplasms
;
Diagnosis
;
Humans
;
Iophendylate
;
Mesencephalon
;
Neurilemmoma*
;
Neuroma, Acoustic
;
Puberty*
;
Trigeminal Nerve
9.Congenital Urinary Tract Anomalies Associated with Urinary Tract Infection in Infants and Children.
Hwa Sook SHIN ; So Hee CHUNG ; Jung Sim KIM ; Hyun Jung KIM ; Mi Na LEE ; Mee Ryung UHM ; Dong Kyu JIN
Journal of the Korean Society of Pediatric Nephrology 1999;3(2):180-186
We report 4 cases of malignant thymoma which were composed of 2 cases of invasive thymoma and 2 cases of thymic carcinoma. The cytologic findings of invasive thymoma were similar to those of benign thymoma. The distinctive cytologic features of thymic carcinoma were necrotic background, irregular clusters and individually scattered arrangement of anaplastic epithelial cells, and some scattered mature small lymphocytes. These findings may be found in the Hodgkin's lymphoma, seminoma, and metastatic squamous cell carcinoma, undifferentiated carcinoma, and large cell carcinoma of the lung. But, the feature of irregular clustering of anaplastic epithelial cell having scanty cytoplasm was different from Hodgkin's lymphoma and seminoma. Clinical and radiologic findings as well as cytologic finding were helpful in differential diagnosis of thymic carcinoma from metastatic carcinoma.
Breast
;
Carcinoma
;
Carcinoma, Large Cell
;
Carcinoma, Squamous Cell
;
Child*
;
Cytoplasm
;
Diagnosis, Differential
;
Epithelial Cells
;
Hodgkin Disease
;
Humans
;
Infant*
;
Lung
;
Lymphocytes
;
Seminoma
;
Thymoma
;
Urinary Tract Infections*
;
Urinary Tract*
10.Erythrocyte Band 7 Integral Protein Defect in Congenital Hemolytic Anemia: Hereditary Stomatocytosis.
Chang Seoup SIM ; Sang Joo HAN ; Hong Jin LEE ; Won Ill PARK ; Kyung Ja LEE ; So Young CHUNG ; Sechan WEE ; Eui Yul CHOI
Journal of the Korean Pediatric Society 1997;40(2):260-265
Hereditary stomatocytosis is a rare congenital hemolytic anemia, named after mouth shaped or stomatocytic erythrocyte morphology. In this report, we present a case of a hereditary stomatocytosis in a 1 month old boy. During the initial identification process, we overlooked the morphology of the RBC in peripheral blood smear and tentatively diagnosed it to be a hereditary spherocytosis case. In order to study further, we isolated RBC membranes from the patient, separated membrane proteins by SDS polyacrylamide gel electrophoresis, and found that a protein band, band 7, was missing in the patient. We suggest that erythrocyte morphology as well as erythrocyte membrane protein analysis is an important criterion in the diagnosis of hereditary hemolytic anemia.
Anemia, Hemolytic, Congenital*
;
Diagnosis
;
Electrophoresis, Polyacrylamide Gel
;
Erythrocyte Membrane
;
Erythrocytes*
;
Humans
;
Infant, Newborn
;
Male
;
Membrane Proteins
;
Membranes
;
Mouth