1.Acquired Drug Resistance during Standardized Treatment with First-line Drugs in Patients with Multidrug-Resistant Tuberculosis.
Doosoo JEON ; Dohyung KIM ; Hyungseok KANG ; Jinhong MIN ; Nackmoon SUNG ; Soohee HWANG ; Seungkew PARK
Tuberculosis and Respiratory Diseases 2009;66(3):198-204
BACKGROUND: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. METHODS: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. RESULTS: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. CONCLUSION: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.
Drug Resistance
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Drug Resistance, Multiple
;
Ethambutol
;
Hospitals, Chronic Disease
;
Humans
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Isoniazid
;
Korea
;
Medical Records
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Nitroimidazoles
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Pyrazinamide
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Retrospective Studies
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Rifampin
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Risk Factors
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Sulfonamides
;
Tuberculosis
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Tuberculosis, Multidrug-Resistant
2.Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma
Kyoungdo MUN ; Jiwon HAN ; Pureun ROH ; Jonggeun PARK ; Gahee KIM ; Wonhee HUR ; Jeongwon JANG ; Jongyoung CHOI ; Seungkew YOON ; Youngkyoung YOU ; Hojoong CHOI ; Pilsoo SUNG
Journal of Liver Cancer 2023;23(2):341-349
Background:
/Aim: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated.
Methods:
Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay.
Results:
CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2.
Conclusions
CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.