OBJECTIVE: To explore the effects of different concentration of pomalidomide on human multiple myeloma cell line MM1.S and the expression of CRBN. METHODS: CCK-8 method was used for detecting inhibition effect of promalidomide on proliferation of MM1.S cells. Apoptosis rate of MM1.S cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Real-time quantitative PCR was used to determine CRBN gene expression level. Western blot was used to detect the effect of pomalidomide on the protein expression of CRBN in MM1.S cells. RESULTS: Pomalidomide has an inhibitory effect on MM1.S cells with time-and dose-dependent manners. Pomalidomide induced apoptosis in MM1.S cells. When the concentration of pomalidomide was 0, 40 and 80 μmol/L, the expression of CRBN gene after the treatment of MM1.S cells for 72 hours was 1.487±0.340, 0.211±0.054 and 0.055±0.005, by using actin as internal refereme. Pomalidomide significantly reduced CRBN protein expression in MM1.S cells. CONCLUSION Pomalidomide can inhibit the proliferation of MM1.S cells and promote its apoptosis. A certain concentration of pomalidomide can reduce the expression of CRBN gene and down-regulate its protein expression in MM1.S cells.
Adaptor Proteins, Signal Transducing ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; Thalidomide ; analogs & derivatives

Lenalidomide, a novel immunomodulatory agent, is a kind of thalidomide derivatives, which shows a good efficacy and safety for hematological system diseases. This review is aimed to evaluate the efficacy and safety of lenalidomide in treatment of patients with multiple myeloma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, classical Hodgkin's lymphoma and POEMS syndrome at their replased or refractory state. At the same time, this review focuses on the newest clinical research and the latest application progress of lenalidomide for relapsed or refractory hematological system diseases.
Antineoplastic Combined Chemotherapy Protocols ; Humans ; Lenalidomide ; Leukemia, Lymphocytic, Chronic, B-Cell ; Lymphoma, Non-Hodgkin ; Multiple Myeloma ; Thalidomide ; analogs & derivatives ; pharmacology

OBJECTIVETo investigate the clinical efficacy of regimen consisting of lenalidomide combined with chemotherapy for acute leukemia and its impact on vascular endothilial growth factor (vEGF) and basic fibroblast growth factor (bFGF), and to analyze the relationship lenalidomide with therapeutic efficacy of leukemia.

METHODSThe patients with newly diagnosed acute myeloid leukemia (except M3) from October 2013 to October 2014 in our hospital were randomly divided into 2 groups: chemotherapy+placebo (CP) group and lenalidomide+chemotherapy (LC) group. In addition, healthy persons were used as healthy controls (HC). The expression of VEGF and bFGF was detected by ELISA, and the therapeutic efficacy for AML patients was analyzed.

RESULTSThe therapeutic efficacy in LC group and CP group was 87.9% and 77.2% respectively. Before treatment, the VEGF level in LC and CP groups was obviously higher than that in HC group; after treatment, the VEGF level significanthy decreased, and the decreased degree in LC group was larger than that in CP group. Before treatment, the bFGF level in LC and CP groups was higher than that in HC group; after treatment, the bFGF level decreased, and decreased degree in LC group was larger than that in CP group.

CONCLUSIONThe lenalidomide combined with chemotherapy can significantly decrease the expression level of VEGF and bFGF, and enhance the remission rate of patients with AML.

Acute Disease ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Thalidomide ; administration & dosage ; analogs & derivatives ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo explore the clinical efficacy and safety of lenalidomide plus low dose dexamethasone for treating patients with multiple myeloma (MM).

METHODSA total of 19 MM patients were enrolled to receive the therapeutic schedule of lenalidomide plus dexamethasone in our hospital from May 2013 to June 2015. Lenalidomide 25 mg was taken orally daily for 21 days and resting for 7 days, and dexamethasone 10 mg was taken orally daily on the day 1-4, 7-10 and 13-16. The regimens were Rd (lenalidomide and dexamethasone, n = 12), and RCd (lenalidomide, ifosfamide and dexamethasone, n = 7).

RESULTSAmong 19 patients received 1 cycle of treatment 3 patients achieved complete remission (CR), 3 patients achieved very good partial remission (VGPR), 10 patients achieved partial remission (PR) and 3 patients in stable disease (SD) with an overall response rate (ORR = CR + VGPR + PR) of 84%; their ORR rate was 89% after 2 cycles of treatment. In the early stage of treatment, the renal function was improved in 4 out of 5 patients with renal dysfunction. And the common adverse reactions were hematologic toxicity in 4 patients, 1 degree rash in 5 patients, and gastrointestinal side effects in 4 patients.

CONCLUSIONThe lenalidomide plus dexamethasone regimen has a good anti-multiple myeloma effect, which can control the disease rapidly and overcome the multidrug resistance in MM, improving the poor prognosis with renal dysfunction, and showing high remission rate in the patients exposed to bortezomib with low toxicity.

Antineoplastic Combined Chemotherapy Protocols ; Dexamethasone ; administration & dosage ; therapeutic use ; Humans ; Ifosfamide ; therapeutic use ; Multiple Myeloma ; drug therapy ; Remission Induction ; Thalidomide ; administration & dosage ; analogs & derivatives ; therapeutic use

OBJECTIVETo explore the clinical features, treatment response and prognosis of multiple myeloma patients aged over 80 years.

METHODSThe clinical data of 23 cases of newly diagnosed multiple myeloma aged over 80 years from February 2007 to July 2014 in our hospital were analyzed retrospectively. The median age was 82, and all the patients had at least 2 complicated diseases. Only 1 patient gave up the chemotherapy because of the poor performance status, the other 22 cases received individualized treatments. Out of 23 patients, 10 received velcade containing regimen (velcade group) chemotherapy, 10 patients received melphalan containing regimen (conventional chemotherapy group) and 2 patients received lenalidomide.

RESULTS1 patient achieved complete remission, 1 patient achieved very good partial remission, 15 patients achieved partial remission, 1 patient achieved minor remission and 4 patients had progressed. Their median survival time was 19.5 months. Their survival rate of one-year, two-years, three-years were 73.9%, 39.1%, 26.1%, respectively. The median OS time and PFS time were 21.5 (9-46) vs 13 (3-23) months (P = 0.405) and 16 (5-38) vs 10 (3-19) months in the velcade group and conventional chemotherapy group, respectively. 9 cases had been alive until December 2015, while 14 cases had died.

CONCLUSIONMultiple meloma patients aged over 80 years diagnosed at advanced stage often accompanied with previous underlined diseases. Treatment should be individualized based on the evaluation of patient status. The OS and PFS time of patients could be prolonged using the velcade containing chemotherapy.

Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bortezomib ; therapeutic use ; Humans ; Melphalan ; therapeutic use ; Multiple Myeloma ; diagnosis ; therapy ; Prognosis ; Remission Induction ; Retrospective Studies ; Survival Rate ; Thalidomide ; analogs & derivatives ; therapeutic use

BACKGROUNDLenalidomide has emerged as an important treatment for patients with multiple myeloma (MM). However, its role in the management of MM is still controversial and requires further clarification. The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.

METHODSWe searched the electronic databases including: PubMed, EMBASE and the Cochrane Center Register of Controlled Trials. Seven randomized clinical trials were identified, which included a total of 2357 patients with MM who received lenalidomide-containing, noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy. The outcomes included overall response (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, and different types of treatment-related adverse events. We calculated the risk ratios (RRs) as well as their 95% confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.

RESULTSFor patients with previously untreated MM, OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group. For relapsed or refractory MM patients, lenalidomide-containing regimens significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate. With regard to MM patients after autologous stem cell transplantation, lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate. In terms of toxicities, lenalidomide therapy has a higher rate of Grade 3-4 grade cytopenias, infection, deep-vein thrombosis, and diarrhea. Furthermore, the incidence of second primary malignancies was significantly higher in the lenalidomide group.

CONCLUSIONSThe lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM. However, when physicians choose to use the lenalidomide as maintenance therapy, whether the benefits outweigh the risks should be taken into account.

Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Humans ; Multiple Myeloma ; drug therapy ; Randomized Controlled Trials as Topic ; Thalidomide ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Multiple myeloma (MM) is an uncurable disease. Chemotherapy with standard dose or autologous stem cell transplantation (auto-HSCT) after chemotherapy with high dose is able to induce remission, but relapse still exists. For this reason the ultimate goal of MM treatment is to improve relapse free survival (RFS) and progression free survival (PFS) efficiently. Recently, maintenance therapy made substantial progress in improving progression-free survival and overall survival (OS) of patients with multiple myeloma, especially thalidomide, lenalidomide and bortezomib used in clinic. Here, the latest advances of clinical researches on maintenance therapy of MM are summarized briefly in this review.
Boronic Acids ; Bortezomib ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Myeloma ; Pyrazines ; Thalidomide ; analogs & derivatives

OBJECTIVETo observe the cytotoxity of CD138-CAR-T cells on human multiple myeloma cell RPMI8226 and U266 cells and explore the impact of pomalidomide on the cytotoxity of CD138-CAR-T on RPMI8226 and U266 cells.

METHODSThe cytotoxity of CD138-CAR-T and CD138-CAR-T combined pomalidomide on RPMI8226 and U266 was detected by CFSE/7AAD. The effctor cells were co-cultured with target cells at 5:1 for 18 h, and then the supernatant were collected and used for ELISA assays.

RESULTSAfter 18 h co-culture, the cytotoxity of CD138-CAR-T on RPMI8226 and U266 was significantiy higher than control (P<0.01). There was no significant change on the cytotoxity of pomalidoide combined with CD138-CAR-T on RPMI8226 and U266. The results showed that co-cultured system contribted to a markedly increased production of IFN-γ, after adding pomalidomide to the co-cultured system. It can significantly enhance the production of IFN-γ, compared with CD138-CAR-T alone.

CONCLUSIONCD138-CAR-T had significantly cytotoxity on U266 and RPMI8226. Pomalidomide could promote CD138-CAR-T cells IFN-γ production.

Cell Line, Tumor ; Coculture Techniques ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multiple Myeloma ; Recoverin ; T-Lymphocytes ; Thalidomide ; analogs & derivatives

In recent years, the incidence of chronic lymphocytic leukemia (CLL) is increasing. Microenvironment and immune system play a key role in the pathogenesis of CLL. The immune system is aggravated by the use of chemotherapeutic agents, such as fludarabine and cyclophosphamide with rituximab(FCR) which are the current standards in frontline therapy. This leads to an increase of infection incidence in patients, resulting in a poor prognosis. The present situation was changed by lenalidomide. Recent studies indicated that lenalidomide monotherapy in treatment of refractory or relapsed CLL patients, the overall response rate(ORR) reached about 32%-47%, CR roughly was 7%-13%; when lenalidomide and rituximab were combined for treatment of refractory or relapsed CLL patients, the ORR reached about 53%-66%, CR about 12%-13%. Moreover, when lenalidomide and ofatumumab were combined, the efficacy is improved significantly and the adverse reactions are greatly reduced. The adverse reactions are neutrophilic granulocytopenia, thrombocytopenia, anemia, tumor lysis syndrome(TLS), tumor flare reaction(TFR) and venous thromboembolism(VTE). This review focuses on the related studies and the latest progress about lenalidomide in CLL.
Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Thalidomide ; adverse effects ; analogs & derivatives ; therapeutic use

cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc. This article reviews the recent progress on PDE4-targeted therapy for inflammatory diseases.
Aminopyridines ; pharmacology ; Aminoquinolines ; pharmacology ; Arthritis ; drug therapy ; Asthma ; drug therapy ; Benzamides ; pharmacology ; Cyclopropanes ; pharmacology ; Dermatitis ; drug therapy ; Humans ; Inflammation ; drug therapy ; Inflammatory Bowel Diseases ; drug therapy ; Phosphodiesterase 4 Inhibitors ; pharmacology ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Sulfones ; pharmacology ; Thalidomide ; analogs & derivatives ; pharmacology ; Thiazoles ; pharmacology