2.Update on treatments of diabetic macular edema.
Xiao-lu YANG ; Kun LIU ; Xun XU
Chinese Medical Journal 2009;122(22):2784-2790
OBJECTIVETo review the update research progress about the treatment of diabetic macular edema and to give helpful guidelines in the treatment of diabetic macular edema based on available evidence to date.Data sources A literature search of all English articles was performed on the online electronic PubMed database dated 1984 to 2009. The keywords searched included: macular edema, therapy, laser coagulation, intravitreal triamcinolone acetonide, vascular endothelial growth factor inhibitor, protein kinase C inhibitor and Pars plana vitrectomy. After finding relevant articles within these search limits, a manual search was conducted through the references from these articles.Study selection Original articles and critical reviews were reviewed and selected to address the stated purpose.
RESULTSTo date, demonstrated means to reduce the risk of vision loss from diabetic macular edema include focal/grid laser photocoagulation and improved metabolic control. Emerging pharmacologic therapies (intravitreal triamcinolone acetonide, vascular endothelial growth factor inhibitors and protein kinase C beta-isoform inhibitors) and Pars plana vitrectomy have shown early promise in the treatment of diabetic macular edema.
CONCLUSIONSAs there has been extensive development in multiple treatments of diabetic macular edema, choice of the most suitable treatment for specific patients becomes important. Combination therapy of laser, pharmacological and surgical treatment modalities may offer an alternative to treatment of diabetic macular edema.
Diabetic Retinopathy ; therapy ; Humans ; Laser Coagulation ; Macular Edema ; therapy ; Protein Kinase C ; antagonists & inhibitors ; Protein Kinase C beta ; Triamcinolone Acetonide ; administration & dosage ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors ; Vitrectomy
3.Data Analysis for Anti-Neoplastic Chemotherapy-Related Adverse Events Reported to the Korean Pharmacovigilance Regional Network.
Ju Yeun LEE ; Jae Woo JUNG ; Hye Ryun KANG ; Se Hoon LEE ; Hyang Sook KIM ; Sang Heon CHO
Korean Journal of Medicine 2013;85(4):385-395
BACKGROUND/AIMS: To describe the toxicity profile of anti-neoplastic agents from real clinical settings, we analyzed spontaneously reported adverse events (AEs) using data from the adverse drug reaction (ADR) reporting system of the Korean Food and Drug Administration (KFDA). METHODS: Data were extracted from the nationwide spontaneous ADR reporting system of KFDA from July 2009 to December 2010. We extracted and analyzed data related to chemotherapy and identified unlabeled ADR that were not described in the package insert of the products. RESULTS: In total, 5,867 cases of antineoplastic agent-related AE reports were identified after excluding cases for duplication and cases assessed as 'unlikely' and 'unclassifiable', based on expert opinion. Of the patients with AEs, 52.4% were males and the median age was 56 years. In total, 460 AEs (7.8%) from 267 patients were reported as 'serious' AEs. The most common causative anti-cancer drug class was pyrimidine analogs (31.5%), followed by platinum compounds (19.9%), protein kinase inhibitors (10.8%), and taxanes (8.8%). The most common clinical manifestation of AEs was gastrointestinal toxicities (25.5%), followed by skin disorders (25.3%), and generalized reactions (14.3%). In total, 168 cases (2.9%) of unlabeled AEs were identified. Among these, 10 were reported as serious AEs. CONCLUSIONS: The most common causative class of antineoplastic agents was that of pyrimidine analogs. Gastrointestinal and dermatological toxicities were the most common clinical chemotherapy-related adverse events. Further investigation and monitoring to evaluate causality associated with unlabeled AEs identified in this analysis are needed.
Antineoplastic Agents
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Drug Toxicity
;
Expert Testimony
;
Humans
;
Male
;
Pharmacovigilance
;
Platinum Compounds
;
Product Labeling
;
Protein Kinase Inhibitors
;
Pyrimidines
;
Skin
;
Statistics as Topic
;
Taxoids
;
United States Food and Drug Administration
4.Data Analysis for Anti-Neoplastic Chemotherapy-Related Adverse Events Reported to the Korean Pharmacovigilance Regional Network.
Ju Yeun LEE ; Jae Woo JUNG ; Hye Ryun KANG ; Se Hoon LEE ; Hyang Sook KIM ; Sang Heon CHO
Korean Journal of Medicine 2013;85(4):385-395
BACKGROUND/AIMS: To describe the toxicity profile of anti-neoplastic agents from real clinical settings, we analyzed spontaneously reported adverse events (AEs) using data from the adverse drug reaction (ADR) reporting system of the Korean Food and Drug Administration (KFDA). METHODS: Data were extracted from the nationwide spontaneous ADR reporting system of KFDA from July 2009 to December 2010. We extracted and analyzed data related to chemotherapy and identified unlabeled ADR that were not described in the package insert of the products. RESULTS: In total, 5,867 cases of antineoplastic agent-related AE reports were identified after excluding cases for duplication and cases assessed as 'unlikely' and 'unclassifiable', based on expert opinion. Of the patients with AEs, 52.4% were males and the median age was 56 years. In total, 460 AEs (7.8%) from 267 patients were reported as 'serious' AEs. The most common causative anti-cancer drug class was pyrimidine analogs (31.5%), followed by platinum compounds (19.9%), protein kinase inhibitors (10.8%), and taxanes (8.8%). The most common clinical manifestation of AEs was gastrointestinal toxicities (25.5%), followed by skin disorders (25.3%), and generalized reactions (14.3%). In total, 168 cases (2.9%) of unlabeled AEs were identified. Among these, 10 were reported as serious AEs. CONCLUSIONS: The most common causative class of antineoplastic agents was that of pyrimidine analogs. Gastrointestinal and dermatological toxicities were the most common clinical chemotherapy-related adverse events. Further investigation and monitoring to evaluate causality associated with unlabeled AEs identified in this analysis are needed.
Antineoplastic Agents
;
Drug Toxicity
;
Expert Testimony
;
Humans
;
Male
;
Pharmacovigilance
;
Platinum Compounds
;
Product Labeling
;
Protein Kinase Inhibitors
;
Pyrimidines
;
Skin
;
Statistics as Topic
;
Taxoids
;
United States Food and Drug Administration
5.Current concepts in the management of rheumatoid arthritis.
The Korean Journal of Internal Medicine 2016;31(2):210-218
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaive, inadequately responsive to methotrexate or tumor necrosis factor (TNF)-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and "deep remission" at the discontinuation was a key factor to keep the treatment holiday of biological DMARD.
Administration, Oral
;
Antirheumatic Agents/*administration & dosage/adverse effects
;
Arthritis, Rheumatoid/diagnosis/*drug therapy/metabolism/physiopathology
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Biological Products/administration & dosage
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Disability Evaluation
;
Drug Administration Schedule
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Humans
;
Janus Kinases/antagonists & inhibitors/metabolism
;
Molecular Targeted Therapy
;
Predictive Value of Tests
;
Protein Kinase Inhibitors/administration & dosage
;
Recovery of Function
;
Remission Induction
;
Signal Transduction/drug effects
;
Treatment Outcome
;
Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism
6.New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis.
Clinical and Molecular Hepatology 2015;21(2):115-121
Despite advances in the treatment of hepatocellular carcinoma (HCC), managing HCC with portal vein thrombosis (PVT) remains challenging. PVT is present in 10-40% of HCC cases at the time of diagnosis and its therapeutic options are very limited. Current guidelines mainly recommend sorafenib for advanced HCC with PVT, but surgery, transarterial chemoemolization, external radiation therapy, radioembolization, transarterial infusion chemotherapy, and combination therapy are also still used. Furthermore, several new emerging therapies such as the administration of immunotherapeutic agents and oncolytic viruses are under investigation. This comprehensive literature review presents current and future management options with their relative advantages and disadvantages and summary data on overall survival.
Carcinoma, Hepatocellular/complications/*pathology/therapy
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Chemoembolization, Therapeutic
;
Combined Modality Therapy
;
Humans
;
Liver Neoplasms/complications/*pathology/therapy
;
Niacinamide/administration & dosage/analogs & derivatives
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Phenylurea Compounds/administration & dosage
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Portal Vein
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Protein Kinase Inhibitors/administration & dosage
;
Venous Thrombosis/complications/*pathology
7.Efficacy and safety of tyrosine kinase inhibitor dasatinib plus chemotherapy in the treatment of childhood Philadelphia chromosome-positive acute lymphoblastic leukemia.
Ye GUO ; Tian-Feng LIU ; Wen-Yu YANG ; Shu-Chun WANG ; Min RUAN ; Xiao-Juan CHEN ; Li ZHANG ; Fang LIU ; Yao ZOU ; Xiao-Fan ZHU
Chinese Journal of Contemporary Pediatrics 2015;17(6):634-637
Antineoplastic Combined Chemotherapy Protocols
;
administration & dosage
;
Child
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Dasatinib
;
Female
;
Humans
;
Male
;
Molecular Targeted Therapy
;
Neoplasm, Residual
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
drug therapy
;
Protein Kinase Inhibitors
;
administration & dosage
;
Protein-Tyrosine Kinases
;
antagonists & inhibitors
;
Pyrimidines
;
administration & dosage
;
adverse effects
;
Thiazoles
;
administration & dosage
;
adverse effects
8.Experimental advance of targeted medicines for chronic myeloid leukemia--review.
Journal of Experimental Hematology 2007;15(1):211-214
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder from hematopoietic stem cell disorder characterized by the consecutive expression of bcr-abl gene, and the translation product of which has enhanced tyrosine kinase activity and can activate a series of downstream signal transduction proteins and results in the occurence of CML. Although the application of imatinib (IM) makes nearly all patients with CML in chronic phase achieve a complete hematologic remission, and 90%of those treated in the early chronic phase achieve a complete cytogenetic remission, but the development of resistance to IM in the course of treatment and even in the beginning of the treatment forced people to develop new agents and to combine the new agents with IM in order to achieve better therapeutic result. This article reviews the experimental advances of targeted therapeutics in CML recent years.
Antineoplastic Agents
;
administration & dosage
;
Benzamides
;
Drug Delivery Systems
;
Humans
;
Imatinib Mesylate
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
;
drug therapy
;
Piperazines
;
administration & dosage
;
Protein Kinase Inhibitors
;
administration & dosage
;
Protein-Tyrosine Kinases
;
antagonists & inhibitors
;
Proto-Oncogene Proteins c-abl
;
biosynthesis
;
genetics
;
Proto-Oncogene Proteins c-bcr
;
biosynthesis
;
genetics
;
Pyrimidines
;
administration & dosage
9.Controlled release of transforming growth factor-beta receptor kinase inhibitor from thermosensitive Chitosan-based hydrogel: application for prevention of capsular contracture.
Zhi-Yong DIAO ; Hai-Liang FU ; Chun-Lei NIE ; Li-Jun HAO ; Da-Ping YANG ; Wei-Hua CHEN
Chinese Medical Journal 2011;124(2):284-290
BACKGROUNDCapsular contracture has become the most common complication associated with breast implant. Transforming growth factor-beta (TGF-β) is well known for a prominent role in fibrotic diseases. Due to the critical role of TGF-β in pathogenesis of capsular formation, we utilized thermosensitive C/GP hydrogel to controlled release of TGF-β receptor kinase inhibitor (SD208) and investigated their effects on capsular contracture.
METHODSIn vitro degradation and drug release of C/GP hydrogel were performed. Twenty-four rabbits underwent subpanniculus implantation with 30 ml smooth silicone implants and were randomly divided into four groups as follows: Group 1 received saline solution; Group 2 received SD208; Group 3 received SD208-C/GP; Group 4 received C/GP. At 8 weeks, the samples of capsular tissues were analyzed by hematoxylin and eosin and immunohistological staining. The mRNA expression of collagen III and TGF-β1 was detected by RT-PCR assay.
RESULTSC/GP hydrogel could be applied as an ideal drug delivery vehicle which supported the controlled release of SD208. SD208-C/GP treatment showed a significant reduction in capsule thickness with fewer vessels. The histological findings confirmed that the lower amounts of inflammatory cells and fibroblasts infiltrate in SD208-C/GP group. In contrast, typical capsules with more vessel predominance were developed in control group. We did not observe the same inhibitory effect of SD208 or C/GP treatment on capsular contracture. Moreover, SD208-C/GP therapy yielded an evident down-regulation of collagen III and TGF-β1 mRNA expression.
CONCLUSIONSThis study demonstrated that controlled release of TGF-β receptor kinase inhibitor from thermosensitive C/GP hydrogel could significantly prevent capsule formation after mammary implants.
Animals ; Breast Implantation ; adverse effects ; Chitosan ; chemistry ; Glycerophosphates ; chemistry ; Hydrogel, Polyethylene Glycol Dimethacrylate ; chemistry ; Immunohistochemistry ; Protein Kinase Inhibitors ; administration & dosage ; therapeutic use ; Rabbits ; Receptors, Transforming Growth Factor beta ; antagonists & inhibitors ; Reverse Transcriptase Polymerase Chain Reaction
10.The effect of chelerythrine on the hypertrophy of cardiac myocytes of neonatal rats induced by different glucose levels and its mechanism.
Wen-Bin ZHANG ; Min WANG ; Bin-Quan ZHOU ; Jun-Hui ZHU ; Guo-Sheng FU
Acta Pharmaceutica Sinica 2009;44(2):115-120
The purpose of this study is to investigate the effect of chelerythrine on the hypertrophy of cardiomyocytes of neonatal rats induced by different glucose levels and its mechanism. Using cultured neonatal ventricular myocytes as a model, groups were divided as: control (5 mmol x L(-1)); high glucose level (10, 15, 20, and 25.5 mmol x L(-1)); high glucose level (25.5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)); and control glucose level (5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)). Different groups of cardiomyocytes after adding corresponding treat factors were cultured for 48 hours. Cardiomyocytes' diameters and protein level were measured and the expression of PKC-alpha, PKC-beta2, p-PKC-alpha, and p-PKC-beta2 were measured by Western blotting. Compared with control group, neonatal myocytes cultured in high glucose levels showed increased cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2. When chelerythrine was added, cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2 were significantly reduced. But in 1 micromol x L(-1) chelerythrine group, the expression of PKC-beta2 was not significantly reduced. The result suggested that chelerythrine can reverse the hypertrophy induced by different glucose levels on the cardiac myocytes, it may have protective effect against diabetic cardiomyopathy via PKC passageway.
Animals
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Animals, Newborn
;
Benzophenanthridines
;
pharmacology
;
Cells, Cultured
;
Diabetes Mellitus, Experimental
;
drug therapy
;
metabolism
;
Dose-Response Relationship, Drug
;
Glucose
;
administration & dosage
;
Hypertrophy
;
chemically induced
;
pathology
;
Hypoglycemic Agents
;
pharmacology
;
Myocytes, Cardiac
;
drug effects
;
pathology
;
Phosphorylation
;
Protein Kinase C
;
antagonists & inhibitors
;
metabolism
;
Protein Kinase C beta
;
Protein Kinase C-alpha
;
metabolism
;
Rats
;
Rats, Sprague-Dawley