OBJECTIVETo evaluate the effect of combination of eicosapentaenoic acid (EPA) and The effects of EPA and epirubicin (EPI) on the human gastric carcinoma cell MGC-803 in vitro.

METHODSEPI were measured by MTT assay , and the interaction between these two agents was evaluated by the isobologram technique of Berenbaum. Morphous of cell was observed by phase-contrast and electron microscope. Flow cytometry was used for cell cycle analysis.

RESULTSEPA significantly inhibited the growth of MGC-803 cells in a dose- and time-dependent way (P < 0.01). Numerous abnormal particles were found around the nucleus of MGC-803 cells under phase-contrast microscope, and also many electron-dense material in cytoplasm were found under electron microscope. EPA significantly stimulated the growth of human embryonal pulmonary fibroblast (HPF) dose-dependently (P < 0.01). A strong synergism was found between EPA and EPI in MGC-803 cells. EPA induced G0/G1-phase arrest but without statistical significance (P > 0.05), and EPI significantly induced S-phase arrest (P < 0.05) in MGC-803 cells.

CONCLUSIONSEPA can inhibit cell growth in gastric carcinoma cells but not in normal cells. EPA and EPI have synergetic effect in the inhibition of gastric carcinoma cells. Compared with EPI monotherapy, the combination of EPI and EPA can reduce the dosage of EPI.

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Arachidonic Acids ; administration & dosage ; Cell Line, Tumor ; Drug Synergism ; Epirubicin ; administration & dosage ; Humans

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

Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM). In the past, clinical data showed that some herbs possessed anticancer properties, but western scientists have doubted the scientific validity of CHM due to the lack of scientific evidence from their perspective. Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of CHM. Experiments showed that CHM played its anticancer role by inducing apoptosis and differentiation, enhancing the immune system, inhibiting angiogenesis, reversing multidrug resistance (MDR), etc. Clinical trials demonstrated that CHM could improve survival, increase tumor response, improve quality of life, or reduce chemotherapy toxicity, although much remained to be determined regarding the objective effects of CHM in human in the context of clinical trials. Interestingly, both laboratory experiments and clinical trials have demonstrated that when combined with chemotherapy, CHM could raise the efficacy level and lower toxic reactions. These facts raised the feasibility of the combination of herbal medicines and chemotherapy, although much remained to be investigated in this area.
Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans

OBJECTIVETo study the reversal effect of tetrandrine (Tet) and droloxifene (Drol) on multidrug resistant cell line K562/A02 and apoptosis induction.

METHODSThe cytotoxicity of daunorubicin (DNR) was assayed by MTT method. The effects of Tet and DRL, alone or combined were detected through the apoptosis of K562/A02 by agarose gel electrophoresis.

RESULTSThe cytotoxicity of DNR to K562/A02 was enhanced by 0.62 microg/ml Tet or 1.94 microg/ml Drol with IC(50) 7.28 +/- 2.06 microg/ml, 7.58 +/- 3.44 microg/ml, giving a reversal effect of 2.94 and 2.82. But IC(50) of combined Tet and Drol was 1.66 +/- 0.41 microg/ml with the reversal effect markedly increased to 12.9. Neither 0.62 microg/ml Tet nor 1.94 microg/ml Drol could induce apoptosis of K562/A02 cells.

CONCLUSIONMultidrug resistance (MDR) can be partially reversed by Tet or Drol, of which the combination shows a great synergistic reversal effect. The mechanism of Tet and Drol reversing multidrug resistance is not correlated with the apoptosis of K562/A02 cells.

Alkaloids ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; Benzylisoquinolines ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; Tamoxifen ; pharmacology ; Tumor Cells, Cultured

OBJECTIVETo assess the feasibility of using MTT assay for detecting the apoptosis of osteosarcoma cells following chemotherapy.

METHODSThe osteosarcoma cells derived form surgical specimens were cultured in RPMI 1640 medium supplemented with 10% calf serum. Chemotherapeutic agents were administered in the cell culture, and MTT assay was used to observe the cell apoptosis under optical microscope.

RESULTSMTT staining accurately identified apoptosis of the osteosarcoma cells, and the apoptotic cells were easily distinguished from normal cells and dead cells.

CONCLUSIONMTT staining is convenient and practical for detecting osteosarcoma cell apoptosis.

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; drug effects ; Bone Neoplasms ; pathology ; surgery ; Humans ; Osteosarcoma ; pathology ; surgery ; Tetrazolium Salts ; Thiazoles ; Tumor Cells, Cultured

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.
Animals ; Mice ; Antineoplastic Combined Chemotherapy Protocols ; Apoptosis Regulatory Proteins ; Colorectal Neoplasms/genetics* ; Fluorouracil/pharmacology* ; Irinotecan/therapeutic use* ; Ki-67 Antigen ; Oxaliplatin ; Proto-Oncogene Proteins p21(ras)/therapeutic use*

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*

Although enumeration of CD34+ cells in the peripheral blood (PB) on the day of apheresis predicts the quantity of those cells collected, the flow cytometric techniques used are complex and expensive, and several hours are required to obtain the result in the clinical practice setting. The Sysmex SE-9000 automated haematology analyzer provides an estimate of immature cells, called hematopoietic progenitor cells (HPC). The aim of this study was to evaluate the clinical usefulness of HPC in predicting the optimal timing of peripheral blood progenitor cells (PBPC) harvest. Studies were performed on 628 aphereses from 160 patients with hematologic or solid malignancies. Spearman's rank statistics was used to assess correlation between HPC, WBC, mononuclear cells (MNC), and CD34+ cells. A receiver operating characteristic (ROC) curve was drawn for cutoff value of HPC, and predictive values of the chosen cutoff value of HPC for different target CD34+ cell collections were calculated. The PB HPC had a stronger correlation (rho=0.592, p<0.001) with collected CD34+ cells than did PB WBC and PB MNC. The ROC curve showed that the best cutoff value of HPC was 50x10(6)/L for the target CD34+ cells >or=1 x10(6)/kg with sensitivity of 75%. Positive and negative predictive values of HPC >or=50x10(6)/L for CD34+ cells >or=1x10(6)/kg were 59.7% and 81.1%, respectively. In the clinical practice setting, applying variable cutoff values of HPC would be a useful tool to predict the optimal timing of PBPC collection.
Adolescent ; Adult ; Antigens, CD34/analysis ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Blood Cell Count*/instrumentation ; Combined Modality Therapy ; Female ; Granulocyte Colony-Stimulating Factor/pharmacology ; Hematopoietic Stem Cell Mobilization* ; Hematopoietic Stem Cells* ; Human ; Leukapheresis* ; Male ; Middle Aged ; Neoplasms/blood ; Neoplasms/drug therapy ; Neoplasms/therapy ; Peripheral Blood Stem Cell Transplantation* ; Predictive Value of Tests ; Sensitivity and Specificity ; Time Factors

Cell apoptosis is an initiative process of cell death regulated by genes. Inducing cell apoptosis is a new way of cancer treatment. In this paper, the progress in experimental studies on the effect of Chinese herbal compounds (CHC) on the induction of tumor cell apoptosis will be reviewed in terms of major mechanisms (gene expression regulation, cell morphology change, telomerase activity change, and immunity enhancement, etc.). The study on disassembled CHC, as well as the synergistic effect when in combined use with chemotherapy for inducing apoptosis, is also reviewed here.
Antineoplastic Agents ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Biomedical Research ; trends ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; enzymology ; pathology ; ultrastructure

Recombinant human-interferon-gamma (rH-IFN-gamma) and verapamil (VRP), either alone or in combination, were evaluated in MTT assay for their modification effects on adriamycin-induced cytotoxicity against MKN-45, human stomach adenocarcinoma cells. VRP as a single agent did not inhibit the survival of MKN-45 at doses of up to 5.0 micrograms/ml. The survival of MKN-45 was inhibited by rH-IFN-gamma dose-dependently and further inhibited by the addition of VRP. However, the maximum growth inhibition of MKN-45 in any combination treatment with rH-IFN-gamma and VRP was less than 50% except in the highest concentration combinations (% survival: 47.9% at 10(4) U/ml of rH-IFN-gamma and 3.0 micrograms/ml of VRP). Adriamycin caused a concentration-dependent cytotoxicity and its cytotoxicity was significantly enhanced by the addition of rH-IFN-gamma and further enhanced by the combined use of rH-IFN-gamma and VRP. The modification effects of rH-IFN-gamma and VRP on adriamycin-induced cytotoxicity were evaluated in terms of modification index (MI), demonstrating that rH-IFN-gamma significantly increased in adriamycin-induced cytotoxicity and that the combined use of rH-IFN-gamma and VRP enhanced the adriamycin-induced cytotoxicity to a greater extent than did rH-IFN-gamma alone: MI values at 10(2) U/ml and 10(3) U/ml of rH-IFN-gamma were 1.7 and 3.1, respectively; those at 1.5 micrograms/ml and 3.0 micrograms/ml of VRP in the presence of 10(3) U/ml of rH-IFN-gamma were 4.4 and 6.0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma/*drug therapy/pathology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Cell Survival/drug effects ; Doxorubicin/*pharmacology ; Drug Interactions ; Drug Resistance ; Drug Screening Assays, Antitumor ; Humans ; Interferon-gamma/*pharmacology ; Recombinant Proteins ; Stomach Neoplasms/*drug therapy/pathology ; Tumor Cells, Cultured ; Verapamil/*pharmacology