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Purpose: Despite significant advances have been achieved in cancer therapy, response to conventional treatments like surgery, radiotherapy and chemotherapy varies among individuals. Immunotherapy is known to be an effective strategy for patients who are resistant to the currently available interventions. Methods: Ninety-six male Balb/c mice (aged 6-8 weeks) were selected and divided into twelve groups of eight. Approximately, 1x106of WEHI-164 cells were injected to each mouse for tumor genesis. Five immunotherapy treatments were considered in this study, including Heat Shock Proteins (HSP), Bacillus Calmette-Guérin (BCG), Bifidobacterium, Immuno-Modulator Drug (IMOD) and Thalidomide. After tumor formation, the groups were treated with one or more of these therapies. Tumor size and survival rate was regularly monitored. Results: Depending on the treatment group, tumor sizes were different. In some groups, combined treatments demonstrated more inhibitory effects on tumor growth rate. The mice in group (IMOD+ Thalidomide) had the lowest survival rate but group (BCG+ HSP+ Thalidomide) survived until the end of the experiment. Conclusion: The (HSP+ BCG+ Thalidomide) group exhibited satisfactory outcomes and two third of the mice in this group went into complete remission. Some combination therapies in test groups had significant impacts on survival and tumor growth rate. [ABSTRACT FROM AUTHOR]

Purpose: The present study, was aimed to assess the cytotoxic effects of Ornithogalum cuspidatum methanolic fractions on PC-3, prostate cancer cells and WEHI-164, Fibrosarcoma cells. Methods: Methanolic fractions of O. cuspidatum were prepared using solid phase extraction and the cells were treated with different concentrations for 12 and 24 hours. Cytotoxicity and cell viability were measured by MTT assay. ELISA was also employed to assess the histone-associated DNA fragments and the involvement of apoptotic mechanisms. Results: 10 and 20% fractions had not significant cytotoxic effects (p>0.05) but other fractions exerted growth inhibition on both cancer cell lines (p<0.05). After 24h of incubation with 40, 60, 80 and 100% fractions, the IC50 values were: 165, 85, 65 and 45μg/ml on PC-3 cells and 200, 96, 76 and 73μg/ml against WEHI-164 cell line, respectively. ELISA results also revealed that, both cell lines had undergone apoptosis. Conclusion: It is deduced that, 80% and 100% methanolic fractions had significant antiproliferative and apoptotic impacts on PC-3 and WEHI-164 cells in vitro and could be considered for developing chemo-preventive substances. [ABSTRACT FROM AUTHOR]

Purpose: Plant-derivate therapeutic agents can perform cancer chemotherapeutic activity through triggering apoptotic cell death. Our aim was to investigate the cytotoxic effects, induction of apoptosis, and the mechanism of cell death of Iranian orthodox black tea extracts (BTEs) and hydro methanolic purified fractions (40, 60, 80 and 100%) in KB cells (oral squamous cell carcinoma). Methods: In order to analyze the cytotoxic activity of the BTEs, MTT (3-(4, 5- dimetylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide) and Trypan-blue assays were performed in oral squamous cell carcinoma (KB). Furthermore, the apoptosis inducing action of the extracts was determined by TUNEL, DNA fragmentation and cell death detection analysis. Results: Dichloromethane BTE and hydro methanol fractions (40 and 60%) extract showed no cytotoxic effects; however, hydro methanol crude and hydro methanol fractions of BTE (80 and 100%) significantly inhibited cell growth and viability in a dose and time dependent manner. In addition, Cell death assay, TUNEL, and DNA fragmentation indicated induction of apoptosis by hydro methanol 80 and 100% fractions of BTE in KB cells. Statistical significance was determined by analysis of variance (ANOVA), followed by Duncan test and p value =0.05 was considered significant. Conclusion: The results from the present study suggests that the hydro methanol crude and hydro methanol fractions of BTE (80 and 100%) are significant source of compounds with the anti proliferative and cytotoxic activities, and this may be useful for developing potential chemo preventive substances. [ABSTRACT FROM AUTHOR]

Metastatic dissemination of the primary tumor is responsible for the majority of cancer-related morbidity and mortality. Detection of disseminated tumor cells in the bone marrow and circulating tumor cells in the peripheral blood is associated with early metastatic recurrence in cancer. Circulating tumor cells (CTCs) shed from the site of disease in metastatic or primary tumor that can be recognized and enriched in the peripheral blood of cancer patients.The detection of rare circulating tumor cells (CTC) is an objective of numerous oncologists' researches. Circulating tumor cells have thepotential to help to detect cancer recurrence at its earlier stage, determine therapy resistance before full blown progression, distinguish molecular changes during treatment, monitor efficacy therapy during treatment, guide therapy choice, and predict clinical outcome. In future perspective, standardization of the different enrichment methods in clinical trial is integrated. Developments in CTC detection methods will improve a wide range of clinical applications, as well as the discovery of biomarkers to predict treatment responses and disease progression. In order to identifying, several techniques have been applied to detect and isolate CTC in a heterogeneous population for management and monitoring response to therapy in clinical course in patients with localized or metastatic disease. [ABSTRACT FROM AUTHOR]

Purpose: CD14, one of the main differentiation markers on the surface of myeloid lineage cells, acts as a key role in activation of LPS-induced monocytes. LPS (lipopolysaccharide) binds to LPS-binding protein in plasma and are delivered to the cell surface receptor CD14. In this study, Various stimuli [Dimethyl Sulfoxide (DMSO), active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and LPS], either alone or in combination, have been recognized that have an effect on the level of CD14 expression in the human HL-60 and U937 promonocytic cell lines and therefore induce their terminal differentiation into monocytes or mature macrophages. Methods: U937 and HL-60 cells were cultured in RPMI 1640 supplemented with 10% FBS. For each cell line, 1×106 cells were seeded for 72 hours with DMSO, 14 days with LPS and 18 days with 1, 25-D3 in each well plate; then ELISA method was used to study their responses to the factors by means of anti-CD14. Results: ELISA assay demonstrated that U937 and HL-60 cells were induced by both [1,25(OH)2D3] and DMSO to obtain characteristics of adherent cells and express CD14 protein; moreover, LPS at a low dose increased CD14 expression on surface of this cells. Conclusion: According to the our results, it is speculated that CD14 gene expression may be induced in human U937 and HL-60 cell lines by different factors including 1,25-D3, DMSO and LPS. [ABSTRACT FROM AUTHOR]

Purpose: Salvia officinalis L., also known as Maryam Goli, is one of the native plants used to Persian medicinal herbs. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized crude methanol extracts prepared from Salvia officinalis L., on a non-Hodgkin's B-cell lymphoma (Raji) and human leukemic monocyte lymphoma (U937), Human acute myelocytic leukemia (KG-1A) and Human Umbilical Vein Endothelial (HUVEC) cell lines. Methods: The effect of methanolic extract on the inhibition of cell proliferation and cytotoxic activity was evaluated by Dye exclusion and Micro culture tetrazolium test (MTT) cytotoxicity assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determined whether the mechanism involves induction of apoptosis or necrosis. Results: The present results demonstrated that methanolic extract at 50 to 800 µg/ml dose and time-dependently suppressed the proliferation of KG-1A, U937 and Raji cells by more than 80% (p<0.01), with ascending order of IC50 values in 24: KG-1A (214.377 µg/ml), U937 (229.312 µg/ml) and Raji (239.692 µg/ml) when compared with a chemotherapeutic anticancer drug, paclitaxel (Toxol), confirming the tumour-selective cytotoxicity. The crude extract however did not exert any significant cytotoxic effect on normal cell line HUVEC (IC50>800 Ag/ml). Nucleosome productions in KG-1A, Raji and U937 cells were significantly increased respectively upon the treatment of Salvia officinalis L. extract. Conclusion: The Salvia officinalis L. extract was found dose and time-dependently inhibits the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway. [ABSTRACT FROM AUTHOR]

Purpose: Monoclonal antibodies are important tools are used in basic research as well as, in diagnosis, imaging and treatment of immunodeficiency diseases, infections and cancers. The purpose of this study was to produce large scale of monoclonal antibody against CD20 in order to diagnostic application in leukemia and lymphomas disorders. Methods: Hybridoma cells that produce monoclonal antibody against human CD20 were administered into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. After twelve days, approximately 7 ml ascetic fluid was harvested from the peritoneum of each mouse. Evaluation of mAb titration was assessed by ELISA method. In the present study, we describe a protocol for large scale production of MAbs. Results: We prepared monoclonal antibodies (mAbs) with high specificity and sensitivity against human CD20 by hybridoma method and characterized them by ELISA. The subclass of antibody was IgG2a and its light chain was kappa. Ascetic fluid was purified by Protein-A Sepharose affinity chromatography and the purified monoclonal antibody was conjugated with FITC and Immunofluorescence was done for confirming the specific binding. Conclusion: The conjugated monoclonal antibody could have application in diagnosis B-cell lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells. [ABSTRACT FROM AUTHOR]

Echinophora platyloba DC plant (Khousharizeh) is one of the indigenous medicinal plants which is used as a food seasoning and medicine in Iran. ?e objective of this study was to examine the in vitro cytotoxic activity and the mechanism of cell death of crude methanolic extracts prepared from Echinophora platyloba DC, on mouse fibrosarcoma cell line (WEHI-164). Cytotoxicity and viability of methanolic extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) assay. Our results demonstrated that the extract decreased cell viability, suppressed cell proliferation, and induced cell death in a time- and dosedependent manner in WEHI-164 cells (IC50 = 196.673 ± 12.4 μg/mL) when compared with a chemotherapeutic anticancer drug, Toxol. Observation proved that apoptosis was the major mechanism of cell death. So the Echinophora platyloba DC extract was found to time- and dose-dependently inhibit the proliferation of fibrosarcoma cell possibly via an apoptosis-dependent pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Targeting CD20 antigen on B-lymphocytes provides good opportunity for management of the target cells in patients with B-cell malignancies. By the advent of hybridoma technology, monoclonal antibodies applications exert extensive changes in medical fields such as diagnosis, treatment and purification. OBJECTIVE: The prim aim of this study was to produce monoclonal antibody against CD20 for exploitation in diagnosis. METHODS: In this study, Balb/c mice were immunized with two peptides from extracellular domain of CD20. Poly Ethylene Glycol (PEG) fused spleen cells of the most immune mouse with SP2/0 (myeloma cells). Supernatant of hybridoma cells were screened for detection of antibody by ELISA. The desired clones were selected for limiting dilution (L.D). Afterward, specificity and cross reactivity of these antibodies were determined by immunological assay such as ELISA and western blot analysis (WB) and Immunofluorescence. Large scale of monoclonal antibodies was produced by ascetic fluid method. Monoclonal antibody was purified by chromatography then confirmed by SDS-PAGE. RESULTS: In this study, between five positive clone wells, 3 clones were chosen for limiting dilution. Limiting dilution product was one monoclone with absorbance about 2. CONCLUSIONS: These results indicate that such monoclonal antibodies against CD20 can be used in diagnosis of CD20 in the cells surface. [ABSTRACT FROM AUTHOR]

The Punica granatum L. var. granatum (pomegranate) has been demonstrated to exert antitumor effects on various types of cancer cells. The present study aimed to evaluate the medicinal herbs Punica granatum L. var. spinosa (apple punice) that are native to Iran. This study was determined to test the possible cytotoxic activity and induction of apoptosis on human prostate cell lines. The effect of ethanol extracts of the herbs on the inhibition of cell proliferation was assessed by MTT colorimetric assay. PC3 cell lines treated with the extracts were analyzed for the induction of apoptosis by cell death detection (ELISA) and TUNEL assay. Dye exclusion analysis was performed for viability rate. Our results demonstrated that the Punica granatum L. var. spinosa extract dose dependently suppressed the proliferation of PC3 cells (IC50= 250.21 µg/mL) when compared with a chemotherapeutic anticancer drug (Toxol) (Vesper Pharmaceuticals) with increased nucleosome production from apoptotic cells. The Punica granatum L. var. spinosa extract attenuated the human prostate cell proliferation in vitro possibly by inducing apoptosis. The Punica granatum L. var. spinosa is likely to be valuable for the treatment of some forms of human prostate cell line [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate in vitro cytotoxic activity of four methanolic crude plant extracts against panel cell lines. Methods: Methanolic extracts were tested for their possible antitumor activity and cytotoxicity using the 3-(4,5-dimetylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay on six cancer cell lines; non-Hodgkin's B-cell lymphoma (Raji), human leukemic monocyte lymphoma (U937), human acute myelocytic leukemia (KG-1A), human breast carcinoma (MCF-7 cells), human Prostate Cancer (PC3) and mouse fibrosarcoma (WEHI-164) cell lines and one normal cell line; Human Umbilical Vein Endothelial Cells (HUVEC). Results: All species showed dose dependent inhibition of cell proliferation. IC50 values ranging from 25.66±1.2 to 205.11±1.3 µg/ml. The highest cytotoxic activity Chelidonium majus L> Ferulago Angulata DC> Echinophora platyloba DC> Salvia officinalis L, respectively. Conclusion: all extracts demonstrate promising cytotoxicity activity as a natural resource for future bio-guided fractionation and isolation of potential antitumor agents. [ABSTRACT FROM AUTHOR]

Behçet Disease (BD) is an autoimmune disorder with recurrent ocular, vascular, central nervous system, articular, mucocutaneous, and gastrointestinal manifestations with unclear etiology and pathogenesis. The further characterization of inflammatory features of Behçet's disease may eventually lead to development of better treatment options. Clinical and laboratory observations suggested an important role of IL-17, IL-21 and neutrophil-mediated process in the pathogenesis of BD. New therapeutic modalities target specific and nonspecific suppression of the immune system. The various non-specific immunosuppressive drugs, used either alone or in combinations, frequently fail to control inflammation or maintain remissions. Due to encouraging clinical results (i.e. Antigenic specification, prolonged survival with acceptable levels of toxicity); antibody-based drugs could be effective for the clinical management of Behçet's disease. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line., Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA) was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and DNA fragmentation gel electrophoresis., Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml). Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis., Conclusions: In summary, the E. platyloba extract attenuated the human prostate adenocarcinoma cell proliferation in vitro possibly by inducing apoptosis. E. platyloba is likely to be valuable for the treatment of human prostate adenocarcinoma.

Human Th17 pro-inflammatory cells are currently defined as cells that produce IL-17A and F, tumor necrosis factor (TNF)-α, IL-6, IL-21, IL-22 and IL-23. Recently discovered related molecules are forming a family of cytokines, the IL-17 family, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. The associated receptors for the IL-17 family identified are IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. This review introduces the roles of IL-17 and Th17 cells in human autoimmune diseases. Studies have shown that T cells with inflammatory effects on epithelial, endothelial and fibroblast cells express IL-17. Th17 cells are supposed to be involved in various autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Base on the biologic functions and regulation, IL-17 has regulatory roles in host defense and chronic inflammation which result in tissue damage and autoimmunity. So the IL-17 links links innate and adaptive immunity and has both beneficial and pathological effects on the immune system. This paper will focus on the possible roles of IL-17 in autoimmune diseases, a fundamental player in immune regulation.

Development of novel therapeutic modalities is crucial for the treatment of oral squamous cell carcinoma (OSCC). Recent scientific studies have been focused on herbal medicines as potent anti-cancer drug candidates. This study is the first to investigate the cytotoxic effects and the mechanism of cell death induced by grape seed extract (GSE) in oral squamous cell carcinoma (KB cells). MTT (3-(4,5-dimetylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) and trypan blue assays were performed in KB cells as well as human umbilical vein endothelial cells (HUVEC) were used to analyze the cytotoxic activity of GSE. Furthermore, the apoptosis-inducing action of the extract was determined by TUNEL, DNA fragmentation and cell death analysis. Statistical significance was determined by analysis of variance (ANOVA), followed by Duncan's test at a significance level of P≤0.05. The results showed apoptotic potential of GSE, confirmed by significant inhibition of cell growth and viability in a dose- and time- dependent manner without inducing damage to non-cancerous cell line HUVEC. The results of this study suggest that this plant contains potential bioactive compound(s) for the treatment of oral squamous cell carcinoma.