Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Dioxoles ; therapeutic use ; Humans ; Sarcoma ; drug therapy ; radiotherapy ; surgery ; Soft Tissue Neoplasms ; drug therapy ; radiotherapy ; surgery ; Tetrahydroisoquinolines ; therapeutic use

Marine antitumor drugs have been the research focus in the world. Recently, advancement has been made in the investigation of six types of compounds including bryostatin-1, ecteinascidin-743, dolastatin, didemnin B, psammaplin and halichondrin B. In this review, we summarized the recent research progress of the above mentioned marine antitumor drugs and their derivatives. Also, the development tendency of marine antitumor drugs was discussed.
Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Biological Products ; isolation & purification ; pharmacology ; therapeutic use ; Bryostatins ; isolation & purification ; pharmacology ; therapeutic use ; Cell Line, Tumor ; drug effects ; Depsipeptides ; isolation & purification ; pharmacology ; therapeutic use ; Dioxoles ; isolation & purification ; pharmacology ; therapeutic use ; Disulfides ; isolation & purification ; pharmacology ; Ethers, Cyclic ; isolation & purification ; pharmacology ; Humans ; Macrolides ; Marine Biology ; Neoplasms ; drug therapy ; pathology ; Tetrahydroisoquinolines ; isolation & purification ; pharmacology ; therapeutic use ; Tyrosine ; analogs & derivatives ; isolation & purification ; pharmacology

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.
Adolescent ; Adult ; Aged ; Alanine Transaminase/*blood ; Cholagogues and Choleretics/*therapeutic use ; Dioxoles/*therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Hepatitis, Alcoholic/*drug therapy ; Hepatitis, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Tertiary Care Centers ; Treatment Outcome ; Ursodeoxycholic Acid/*therapeutic use ; Young Adult

Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.
Antineoplastic Agents, Alkylating ; therapeutic use ; Clinical Trials as Topic ; DNA Damage ; Dioxoles ; administration & dosage ; pharmacology ; therapeutic use ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Neoplasm Recurrence, Local ; drug therapy ; Neoplasms, Glandular and Epithelial ; drug therapy ; Ovarian Neoplasms ; drug therapy ; Polyethylene Glycols ; administration & dosage ; Tetrahydroisoquinolines ; administration & dosage ; pharmacology ; therapeutic use ; Tumor Microenvironment

AIMTo study the effect of antihepatitis drug, dimethyl diphenyl bicarboxylate (DDB) on the metabolism and hepatotoxicity of aflatoxin B1(AFB1) in rats.

METHODSRats were given orally DDB 300 mg.kg-1.d-1 for 3 days and then injected intraperitioneally with AFB1 1.5 mg.kg-1. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined 16 hours after the injection of AFB1. The in vitro metabolism of AFB1 by DDB-pretreated rat liver microsome was investigated by HPLC assay.

RESULTSDDB (300 mg.kg-1) pretreatment provided significant protection against AFB1 hepatotoxicity as evidenced by the decrease of AFB1-elevated serum marker enzymes in rats. Pretreatment with DDB was shown to slightly increase the level of AFM1, the less toxic metabolite. DDB significantly increased the liver cytochrome P450 content, P450 isozyme 2B1-mediated 7-pentoxyresorufin O-dealkylase (PROD) activity, cytosolic glutahione (GSH) level and GSH S-transferase (GST) activities. In addition, DDB slightly increased P450 isozymes, 3A-mediated erythromycin-demethylase and 1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activities.

CONCLUSIONThe results indicate that DDB protected rats against AFB1 hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver.

Aflatoxin B1 ; pharmacokinetics ; toxicity ; Aflatoxin M1 ; metabolism ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Biotransformation ; Chemical and Drug Induced Liver Injury ; etiology ; metabolism ; prevention & control ; Cytochrome P-450 Enzyme System ; metabolism ; Dioxoles ; therapeutic use ; Disease Models, Animal ; Male ; Microsomes, Liver ; metabolism ; Protective Agents ; therapeutic use ; Rats

OBJECTIVETo study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA).

METHODSWistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent.

RESULTSCompared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.

CONCLUSIONOur data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.

Animals ; Arthritis, Experimental ; chemically induced ; diagnostic imaging ; drug therapy ; pathology ; Arthritis, Rheumatoid ; diagnostic imaging ; drug therapy ; pathology ; Collagen ; Cyclooxygenase 2 ; blood ; Dioxoles ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Female ; Interleukin-4 ; blood ; Interleukin-8 ; blood ; Methotrexate ; therapeutic use ; Nitric Oxide ; biosynthesis ; Platelet-Derived Growth Factor ; analysis ; Radiography ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood ; Vascular Endothelial Growth Factor A ; blood