Anti-Tumour Effects of Exosomes in Combination with Cyclophosphamide and Polyinosinic–Polycytidylic Acid

2008 ◽  
Vol 36 (6) ◽  
pp. 1342-1353 ◽  
Author(s):  
F Guo ◽  
CK Chang ◽  
HH Fan ◽  
XX Nie ◽  
YN Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poly I:C ◽  
Spleen Cells ◽  
Polycytidylic Acid ◽  
Anti Tumour Activity ◽  
Anti Cancer ◽  
Tumour Activity ◽  
Dc Maturation ◽  
Polyinosinic Polycytidylic Acid

We examined the anti-tumour activity of exosomes derived from dendritic cells (DCs) in combination with cyclophosphamide (CTX) and polyinosinic–polycytidylic acid sodium salt (poly I:C). DCs were pulsed with L1210 lymphocytic leukaemia cell antigen and lipopolysaccharide. The exosomes that the DCs secreted were purified. In vitro, the anti-tumour activity of exosomes was assessed by measuring their ability to induce spleen cell proliferation and the extent to which they induced spleen cells to kill L1210 cells. Poly I:C was able to induce DC maturation. DC-derived exosomes stimulated spleen cell proliferation and enhanced the cytotoxic effects of spleen cells in vitro. DC-derived exosomes, in combination with CTX and poly I:C, suppressed L1210 tumour growth in vivo and gave the greatest prolongation of survival time in tumour-bearing DBA2 mice. These findings suggest that this combination of a tumour vaccine, a conventional anti-cancer agent and a promoter of DC maturation might be a useful anti-cancer therapy.

Killing cancer cells using nanotechnology: novel poly(I:C) loaded liposome–silica hybrid nanoparticles

2015 ◽  
Vol 3 (37) ◽  
pp. 7408-7416 ◽  
Author(s):  
Valentina Colapicchioni ◽  
Sara Palchetti ◽  
Daniela Pozzi ◽  
Elettra Sara Marini ◽  
Anna Riccioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hybrid Nanoparticles ◽  
Poly I:C ◽  
Core Shell ◽  
Polycytidylic Acid ◽  
Anti Cancer ◽  
Polyinosinic Polycytidylic Acid ◽  
Silica Hybrid

Synthesized core–shell liposome–silica hybrid nanoparticles (LSH NPs), when loaded with the anti-cancer polyinosinic–polycytidylic acid (poly(I:C)), exhibit high anti-tumoral activity in prostate and breast cancer cells.

Effect of Polyinosinic-polycytidylic Acid on Humoral and Cellular Immunity

1973 ◽  
Vol 59 (2) ◽  
pp. 77-96 ◽  
Author(s):  
Dino Collavo ◽  
Giovanni Biasi ◽  
Natale Pennelli ◽  
Luigi Chieco-Bianchi
Keyword(s):  
Immune Response ◽  
Germinal Centers ◽  
The Other ◽  
Poly I:C ◽  
Secondary Response ◽  
Spleen Cells ◽  
Humoral And Cellular Immunity ◽  
Polycytidylic Acid ◽  
Other Hand ◽  
Polyinosinic Polycytidylic Acid

Experiments have been performed to investigate the effects of polyinosinic-polycytidylic acid (Poly I:C) on humoral and cellular immunity in RFM/Un mice. Poly I:C, 0.1 mg i.p., administered 48 and 24 hours before 4 x 108 SRBC produced a marked reduction in direct PFC/106 cells and /spleen, and in the hemoagglutinin titre on the 3rd, 4th and 5th days after antigen inoculation. On the other hand, an increase in PFC and hemoagglutinin titre was observed on the 7th and 8th days. Histological examination revealed absence of germinal centers in the spleen on the 4th day. Poly I:C administered 24 and 48 hours after antigen produced an increase in direct PFC and hemoagglutinin titre on the 4th, 5th and 6th day. Histological examination disclosed evident germinal centers in the spleen on the 4th day after antigen. Poly I:C administered 5 to 1 days before antigen produced a markedly depressed direct PFC response in the groups injected 1 and 2 days before antigen. Recovery of the immune response was progressive and complete in groups injected 4 days before antigen. To study the effect of Poly I:C on secondary response to SRBC, two groups of animals injected with Poly I:C before or after antigen were reinjected with 2 x 108 SRBC. Secondary response evaluated by hemoagglutinin titre at varying intervals after the immunization disclosed in both groups a much higher antibody titre than that seen in controls receiving SRBC only. Mice injected with Poly I:C 48 or 24 hours before reimmunization with 2 x 108 SRBC were no different from controls on 3rd and 4th days in regard to number of indirect PFC as well as hemoagglutinin titre. Finally, mice immunized with two SRBC injections and then treated with Poly I:C on alternating days for 30 days had a much higher titre of hemoagglutinins than controls. In order to study the effect of Poly I:C on the cellular immune response, spleen cells from animals receiving Poly I:C 6–5 days before sacrifice were cultured in vitro with phytohemoagglutinin. DNA synthesis subsequent to PHA stimulation was evaluated by increase in 3HTdR incorporation. Cells from animals which had received Poly I:C demonstrated a remarkably higher 3HTdR uptake than cells from control animals. On the other hand, 5 x 106 spleen cells obtained from RFM/Un mice injected with Poly I:C as above were inoculated in 1–4 day old (RFM/Un x CBA/H)F1 hybrids. These were then sacrificed on day 8 and spleen indices calculated. Experimental animals disclosed GVH activity similar to that of controls (spleen index 2.3). From the results it is clear that if Poly I:C is injected before antigen the primary immune response is deppressed, whereas it is enhanced when Poly I:C is administered after antigen. On the other hand, the secondary response is generally enhanced regardless of the time of Poly I:C administration. Moreover, in Poly I:C –- treated animals there is an enhancement of PHA –- responsive cells while the GVH reactions is unchanged. As Poly I:C is capable of enhancing immune reactivity, the possibility of its use in antineoplastic chemotherapeutic protocols is suggested.

Protective Action of Polyinosinic-Polycytidylic Acid in Virus and Transplanted Leukemias of the Mouse

1973 ◽  
Vol 59 (3) ◽  
pp. 167-179
Author(s):  
Luigi Chieco-Bianchi ◽  
Dino Collavo ◽  
Giovanni Biasi ◽  
Alfonso Colombatti
Keyword(s):  
Protective Action ◽  
Immunological Tolerance ◽  
Leukemic Cells ◽  
Poly I:C ◽  
Immune Reactivity ◽  
Cell Transplant ◽  
Adult Mice ◽  
Polycytidylic Acid ◽  
Polyinosinic Polycytidylic Acid

The inhibitory effects of polynucleotides on leukemia development and transplantability have been studied. RFM/Un mice, injected neonatally with leukemogenic Graffi virus, received 0.02 mg polyinosinic-polycytidylic acid (Poly I:C) intraperitoneally, twice a week, for two months starting 24 hrs after virus injection. Leukemia incidence in treated mice was significantly reduced, i.e., 56% with a mean latent period of 19 weeks as compared to 87% and 15 weeks latency in the control animals. RFM/Un adult mice, injected intravenously with different cell doses of two transplantable syngeneic leukemias, received four doses of 0.1 mg Poly I:C on alternate days starting 24 hrs after cell transplant. The evaluation of neoplastic nodules on the spleen surface according to the method of Bruce and Van Der Gaag (2) was the parameter of leukemic growth. Mice receiving Poly I:C showed a marked reduction in spleen nodule counts for all cell doses of both leukemia lines and histological examination of the spleen confirmed actual decrease in leukemic foci and disclosed enlargement of germinal centers and periarteriolar areas of lymphoid follicles. To investigate whether Poly I:C is capable of abolishing the state of immunological tolerance (operationally speaking) to cellular virus-induced antigens (CBA x C57BL)F1 adult mice, injected neonatally with Graffi virus, received 0.20 mg Poly I:C i.p. together with 104 or 105 cells from a syngeneic transplantable leukemia originally induced by Graffi virus. No differences in leukemic deaths were observed between Poly I:C treated virus-injected animals and controls, even though normal mice receiving Poly I:C and 10* cells showed 50% survival compared to 0% in control groups. Leukemic cells incubated in vitro in HE-MEM containing 0.1, 1, 10 or 100 μg Poly I:C/ml for 2, 4, 8 and 24 hrs (37 °C, 5% CO2) did not exhibit significant changes in viability as evaluated by phase contrast microscopy. On the basis of present and previous results (6), the possible mechanisms of antineoplastic action exerted by polynucleotides are discussed. It is concluded that while interferon production by synthetic RNAs may represent a major inhibiting factor in virus-induced tumors, non specific stimulation of immune reactivity and direct effect on cell metabolism and replication may play a significant role in other neoplastic conditions.

scholarly journals Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway

2021 ◽  
pp. 096032712110544
Author(s):  
Zi-tan Peng ◽  
Pei Gu
Keyword(s):  
Cell Proliferation ◽  
Gastric Carcinoma ◽  
Carcinoma Cells ◽  
Malignant Progression ◽  
Gastric Carcinoma Cell ◽  
Over Expression ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Cruciferous Plants

Objective Sulforaphane, which exerts an effective anti-cancer ability, is a phytochemical converted from cruciferous plants. Here, we aimed to identify whether sulforaphane could suppress autophagy during the malignant progression of gastric carcinoma and to explore the underlying mechanisms. Methods SGC7901 cells were transfected with miR-4521 mimics, inhibitor, and pcDNA3.1- PIK3R3, and treated with sulforaphane or autophagy inhibitor. Cell proliferation, apoptosis, and miR-4521 or PIK3R3 expression were detected. Results MiR-4521 over-expression suppressed LC3-II/I ratio and Beclin-1 expression but induced p62 expression in SGC7901 cells. MiR-4521 also reduced gastric carcinoma cell proliferation and promoted apoptosis in vitro. In the mechanical observation, we identified that miR-4521 directly targeted PIK3R3 to repress its expression, and PIK3R3 up-regulation partly antagonized miR-4521-mediated autophagy, proliferation, and apoptosis in gastric carcinoma cells. In addition, sulforaphane exerted effective anti-cancer functions by repressing autophagy and growth in tumor cells at a concentration-dependent way. MiR-4521 inhibition or PIK3R3 over-expression weakened the anti-cancer functions of sulforaphane in gastric carcinoma cells. Conclusion Consequently, miR-4521 suppressed autophagy during the malignant progression of gastric carcinoma by targeting PIK3R3. Thus, miR-4521 may be applied as a therapeutic target for sulforaphane in gastric carcinoma.

scholarly journals Basolateral activation with TLR agonists induces polarized cytokine release and reduces barrier function in RPE in vitro

2020 ◽  
Author(s):  
Laura Terheyden ◽  
Johann Roider ◽  
Alexa Klettner
Keyword(s):  
Cell Viability ◽  
Barrier Function ◽  
Neuronal Cell ◽  
Poly I:C ◽  
Rpe Cells ◽  
Ussing Chambers ◽  
Tlr Agonists ◽  
Danger Signals ◽  
Polycytidylic Acid

Abstract Purpose Systemic inflammation may be of importance in the development of AMD. RPE cells can recognize danger signals with toll-like receptors (TLR) and may react in a pro-inflammatory manner. In this study, we evaluated the basal and apical secretions of TNFα, IL-6, and IL-1β in primary RPE cells and RPE/choroid explant cells under basolateral stimulation of TLR2, 3, and 4; the effects on barrier function; and their influence on neuronal cell viability. Methods RPE/choroid tissue explants were prepared from porcine eyes and cultivated in modified Ussing chambers; primary porcine RPE cells on transwell plates. Cells were basally stimulated with agonists Pam2CSK4 (Pam; TLR2), polyinosinic/polycytidylic acid (Poly I:C; TLR3), and lipopolysaccharide (LPS; TLR4) for 24 h. Supernatants were evaluated with ELISA for cytokines TNFα, IL-6, and IL-1β. Apical supernatants were applied to SHSY-5Y cells, and cell viability was evaluated in MTT assay. Barrier function was tested by measuring transepithelial electrical resistance (TER) and occludin immunostaining. Results None of the tested TLR agonists was toxic on RPE cells after 24 h of exposure. Unstimulated RPE cells secreted hardly any cytokines. Pam induced IL-6, IL-1ß, and TNFα on the basal and apical sides at all concentrations tested. Poly I:C induced IL-6 and TNFα primarily at the basal side at lower but on both sides at higher concentrations. LPS induced IL-6, IL-1ß, and TNFα apically and basally at all concentrations tested. In the RPE/choroid, a strong difference between apical and basal secretions could be found. IL-6 was constitutively secreted basally, but not apically, but was induced by all agonists on both sides. IL-1ß and TNFα alpha were strongly induced on the basal side by all agonists. TER was reduced by all agonists, with Pam and LPS being effective in all concentrations tested. Occludin expression was unaltered, but the distribution was influenced by the agonists, with a less distinct localization at the cell borders after treatment. None of the agonists or supernatants of treated RPE and RPE/choroid organ cultures exerted any effect on viability of SHSY-5Y cells. Conclusions Danger signals activating TLRs can induce polarized cytokine expression and contribute to the loss of barrier function in the RPE.

scholarly journals Polyinosinic: Polycytidylic Acid and Murine Cytomegalovirus Modulate Expression of Murine IL-10 and IL-21 in White Adipose Tissue

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 569
Author(s):  
Pablo Garcia-Valtanen ◽  
Ruth Marian Guzman-Genuino ◽  
John D. Hayball ◽  
Kerrilyn R. Diener
Keyword(s):  
Adipose Tissue ◽  
B Cells ◽  
White Adipose Tissue ◽  
Ex Vivo ◽  
Interleukin 10 ◽  
Poly I:C ◽  
Murine Cytomegalovirus ◽  
Polycytidylic Acid ◽  
Polyinosinic Polycytidylic Acid

White adipose tissue (WAT) produces interleukin-10 and other immune suppressors in response to pathogen-associated molecular patterns (PAMPs). It also homes a subset of B-cells specialized in the production of IL-10, referred to as regulatory B-cells. We investigated whether viral stimuli, polyinosinic: polycytidylic acid (poly(I:C)) or whole replicative murine cytomegalovirus (MCMV), could stimulate the expression of IL-10 in murine WAT using in vivo and ex vivo approaches. Our results showed that in vivo responses to systemic administration of poly(I:C) resulted in high levels of endogenously-produced IL-10 and IL-21 in WAT. In ex vivo WAT explants, a subset of B-cells increased their endogenous IL-10 expression in response to poly(I:C). Finally, MCMV replication in WAT explants resulted in decreased IL-10 levels, opposite to the effect seen with poly(I:C). Moreover, downregulation of IL-10 correlated with relatively lower number of Bregs. To our knowledge, this is the first report of IL-10 expression by WAT and WAT-associated B-cells in response to viral stimuli.

scholarly journals 3′,4′-Dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening

2020 ◽  
Vol 7 (1) ◽  
pp. 191316 ◽  
Author(s):  
Maloba M. M. Lobe ◽  
Simon M. N. Efange
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Biological Activities ◽  
Cell Cancer ◽  
Breast Cancer Cell Lines ◽  
Small Cell Lung ◽  
Preliminary Screening ◽  
Anti Cancer ◽  
Molecular Hybrids

Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities including anti-cancer activity, and are therefore recognized as two privileged scaffolds in drug discovery. In the present study, 24 3′,4′-dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones, designed as molecular hybrids of THIQ and OX, were synthesized and screened in vitro against 59 cell lines in the NCI-60 screen. Twenty compounds displayed weak to moderate inhibition of cell proliferation; among them, three compounds displayed at least 50% inhibition of cell proliferation. The compounds appeared to target primarily renal cell cancer lines; however, leukaemia, melanoma, non-small cell lung cancer, prostate, ovarian and even breast cancer cell lines were also affected. Therefore, this class of spirooxindoles may provide useful leads in the search for new anti-cancer agents.

scholarly journals The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 427 ◽  
Author(s):  
Ranjini Sankaranarayanan ◽  
Chaitanya Valiveti ◽  
D. Kumar ◽  
Severine Van slambrouck ◽  
Siddharth Kesharwani ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell Proliferation ◽  
Cyclin Dependent Kinase ◽  
Specific Amino Acid ◽  
In Silico Studies ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
First Time ◽  
Related Compounds

Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora. In this study, we investigated the ability of one metabolite, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions. Interestingly, no significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that orientation of the functional groups and specific amino acid interactions may play a role in inhibition. We showed that cellular uptake of 2,4,6-THBA required the expression of functional SLC5A8, a monocarboxylic acid transporter. Consistent with this, in cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21Cip1 and p27Kip1 and inhibited cell proliferation. These findings, for the first time, suggest that the flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway contributing to the prevention of CRC.

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