Non-Hodgkin lymphoma (NHL) is a common lymphoid hematological malignancy, the treatment and prognosis of NHL have always been the focus of clinical attention. Chemotherapy is the main first-line treatment, but there is still no effective treatment for patients with poor response to chemotherapy, recurrence or progression within a short period of time after treatment, and new and effective drugs need to be developed clinically. As the only clinically validated oral selective inhibitor of nuclear export (SINE), Selinexor has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma and multiple myeloma, clinical attempts are being made to apply it to the treatment of other hematological malignancies.This article reviews the anti-tumor mechanism of Selinexor and the latest research progress in its application in NHL, and provides ideas for a more diverse, standardized and effective applications of Selinexor in NHL.
Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Active Transport, Cell Nucleus ; Hydrazines/pharmacology* ; Triazoles/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Candidemia due to uncommon Candida spp. appears to be increasing in incidence. C. dubliniensis has been increasingly recovered from individuals not infected with HIV. Identification of C. dubliniensis can be problematic in routine clinical practice due to its phenotypic resemblance to C. albicans. We report the first case of C. dubliniensis candidemia in Korea, which occurred in a 64-yr-old woman who presented with partial seizure, drowsiness, and recurrent fever. Germ-tube positive yeast that was isolated from blood and central venous catheter tip cultures formed smooth, white colonies on sheep blood agar and Sabouraud agar plates, indicative of Candida spp. C. dubliniensis was identified using the Vitek 2 system (bioMerieux, USA), latex agglutination, chromogenic agar, and multiplex PCR. The blood isolate was susceptible to flucytosine, fluconazole, voriconazole, and amphotericin B. After removal of the central venous catheter and initiation of fluconazole treatment, the patient's condition gradually improved, and she was cleared for discharge from our hospital. Both clinicians and microbiologists should be aware of predisposing factors to C. dubliniensis candidemia in order to promote early diagnosis and appropriate treatment.
Amphotericin B/pharmacology ; Antifungal Agents/pharmacology/therapeutic use ; Candida/drug effects/*isolation & purification ; Candidemia/*diagnosis/drug therapy ; Catheterization, Central Venous ; Female ; Fluconazole/pharmacology/therapeutic use ; Flucytosine/pharmacology ; Humans ; Microbial Sensitivity Tests ; Middle Aged ; Pyrimidines/pharmacology ; Triazoles/pharmacology

In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.
Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Fungi ; drug effects ; Heterocyclic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Lipopeptides ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Mycoses ; drug therapy ; Nitriles ; chemistry ; pharmacology ; therapeutic use ; Plant Extracts ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Pyridines ; chemistry ; pharmacology ; therapeutic use ; Quinazolines ; chemistry ; pharmacology ; therapeutic use ; Quinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Thiazoles ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use

In the two decades since AZT was first approved for clinical use in 1987, 24 additional antiretroviral agents have been approved. They include 7 nucleoside analogs, a nucleotide analog and 4 non-nucleoside reverse transcriptase inhibitors, 10 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. More than 20 investigational agents are currently being studied in clinical trials. Highly active antiretroviral therapy (HAART), which involves a combination of anti-HIV-1 drugs, is extremely effective in suppressing HIV-1 replication and increasing CD4+ number and results in substantial reductions in HIV-1-related morbidity and mortality. In last 20 years, much has been learned about resistance to antiretroviral drugs, drug interactions and metabolic complications of antiviral drug use. Drugs are now selected on the basis of resistance tests and on the risk of specific drug complications in individual patients. As a result, decisions about the therapy of HIV/AIDS have become personalized and are made on a patient-by-patient basis. With appropriate medical management, a person with HIV-1 now has the possibility of a nearly normal life expectancy.
Anti-HIV Agents ; adverse effects ; pharmacology ; therapeutic use ; Antiretroviral Therapy, Highly Active ; Cyclohexanes ; chemistry ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; HIV Envelope Protein gp41 ; chemistry ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Reverse Transcriptase ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; physiology ; Humans ; Molecular Structure ; Peptide Fragments ; chemistry ; therapeutic use ; Pyrrolidinones ; chemistry ; pharmacology ; therapeutic use ; Raltegravir Potassium ; Saquinavir ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use ; Virus Replication ; drug effects ; Zidovudine ; chemistry ; pharmacology ; therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

This review discusses recent progress in the development of anti-HIV agents, with emphasis on small molecule HIV-1 entry inhibitors. The entry inhibitors primarily target HIV-1 envelope glycoproteins or the cellular receptors, CD4 and chemokine receptors. Two of the entry inhibitors, enfuvirtide and maraviroc, have been approved by the US FDA for AIDS therapy. The drug resistance associated with some of the entry inhibitors will also be discussed.
Anti-HIV Agents ; chemistry ; pharmacology ; therapeutic use ; CCR5 Receptor Antagonists ; CD4 Antigens ; drug effects ; Cyclohexanes ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; HIV Envelope Protein gp120 ; pharmacology ; HIV Envelope Protein gp41 ; pharmacology ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Peptide Fragments ; pharmacology ; therapeutic use ; Receptors, CCR5 ; physiology ; Receptors, CXCR4 ; antagonists & inhibitors ; Receptors, Chemokine ; drug effects ; Triazoles ; pharmacology ; therapeutic use

AIM: To evaluate the effect of Cocus nucifera L. flowers in reducing the major multiple symptoms of letrozole-induced polycystic ovarian disease (PCOD) in female rats. METHOD: Female, virgin Wistar rats were treated with letrozole (1 mg/kg body wt) to induce PCOD, and after 21 days of induction rats were administered orally with 100 and 200 mg·kg(-1) of Cocus nucifera flower aqueous extract, respectively. Estrus cycle and blood sugar were monitored once a week throughout the study. After scarification, various biochemical parameters, such as antioxidant status (superoxide dismutase (SOD) and glutathione reductase (GSH)) of the uterus homogenate, lipid profile (total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides (TG)) of the serum were determined. Weights of the uterus and ovaries were separately monitored. The characteristics of changes in the ovary were evaluated by histopathological studies. RESULTS: GC-MS analysis of the aqueous extract showed the presence of volatile and pharmacologically active phytoconstituents. C. nucifera flower extract-treated groups showed estrus cyclicity and increased uterus weight which indicates the estrogenic effect. The improved blood sugar level, ideal lipid profile, good antioxidant status, and histopathology results revealed the recovery from poly cystic ovaries. CONCLUSION The results indicate that C. nucifera flower is a potential medicine for the treatment of PCOD and this study supports the traditional uses of C. nucifera flower.
Animals ; Antioxidants ; metabolism ; Blood Glucose ; metabolism ; Cocos ; chemistry ; Estrus ; drug effects ; Female ; Flowers ; chemistry ; Gas Chromatography-Mass Spectrometry ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Letrozole ; Lipids ; blood ; Nitriles ; Oils, Volatile ; analysis ; pharmacology ; therapeutic use ; Ovary ; drug effects ; pathology ; Phytoestrogens ; pharmacology ; therapeutic use ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Polycystic Ovary Syndrome ; blood ; chemically induced ; drug therapy ; pathology ; Rats, Wistar ; Triazoles ; Uterus ; drug effects

Aromatase is a key enzyme responsible for in vivo estrogen biosynthesis. Inhibition of the activity of the aromatase has become an alterative way for treatment of breast cancer. In this review, the structure and catalytic mechanism of the aromatase is briefly introduced followed by thorough review of the progress in the study of the steroidal and non-steroidal aromatase inhibitors. This review is focused on the natural compounds that exhibit the aromatase inhibition, which include flavonoids, xanthones, coumarins, and sesquiterpenes. The structure-activity relationship of these compounds is also discussed.
Androstenedione ; analogs & derivatives ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Aromatase ; chemistry ; metabolism ; pharmacology ; Aromatase Inhibitors ; chemistry ; classification ; pharmacology ; therapeutic use ; Breast Neoplasms ; drug therapy ; Catalysis ; Coumarins ; chemistry ; pharmacology ; Estrogens ; biosynthesis ; Flavonoids ; chemistry ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Nitriles ; chemistry ; pharmacology ; Sesquiterpenes ; chemistry ; pharmacology ; Structure-Activity Relationship ; Triazoles ; chemistry ; pharmacology ; Xanthones ; chemistry ; pharmacology

Apoptosis ; drug effects ; Benzoquinones ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; pathology ; Drug Resistance, Neoplasm ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; Humans ; Lactams, Macrocyclic ; pharmacology ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Mutation ; Oncogene Proteins, Fusion ; antagonists & inhibitors ; genetics ; metabolism ; Protein Kinase Inhibitors ; therapeutic use ; Pyrazoles ; therapeutic use ; Pyridines ; therapeutic use ; Triazoles ; pharmacology