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Here, we investigated the effects of dual delivery of IGF-1R siRNA and doxorubicin by chitosan nanoparticles on viability of A549 lung cancer cells line by utilization of MTT and qRT-PCR. Furthermore apoptosis and migration of treated cells were assessed by Annexin-PI and wound healing assays, respectively. The chitosan nanoparticles had about 176 nm size with zeta potential and polydispersive index about 11 mV and 0.3, respectively. The IGF-1R siRNA had synergistic effect on DOX-induced cytotoxicity and apoptosis in tumour cells. In addition, siRNA/DOX-loaded chitosan nanoparticles could significantly decrease migration and expressions of mmp9, VEGF and STAT3 in A549 cells. [ABSTRACT FROM AUTHOR]

Background:Extracellular signal-regulated kinase (Erk)1 and Erk2 are central mediators of mitogen-activated protein kinase signaling pathway, which plays a key role in proliferation and chemoresistance of cancer cells. However, the effect of Erk1 and Erk2 in these processes may not be the same. The aim of this study was to investigate differential effect of Erk1 and Erk2 down-regulation on chemoresistance in human hepatocellular carcinoma (HCC) cells. Expression level and relative expression analysis in HepG2 cells were performed using RT-PCR and qRT-PCR, respectively. Phosphorylated-Erk1/2 and apoptosis analysis was performed by flow-cytometry (FCM) technique. Results:The results showed a higher expression level of Erk2 relative to Erk1 in HepG2 cells (P < 0.01). A significant decrease in phosphorylated-Erk1/2 and a compensational response was observed after Erk1 and/or Erk2 silencing using specific small interfering ribonucleic acids (siRNAs) (P < 0.01). Furthermore, 5-fluorouracil (5-FU) chemotherapy following siRNA-mediated knockdown lead to a significant enhancement of chemosensitivity with a higher rate of early apoptosis in Erk2 silencing relative to that of Erk1) + 9%,P < 0.01). 5-FU treatment after dual knockdown of Erk1/2 showed higher rate of early apoptosis relative to single Erk1 silencing (+9.25%,P < 0.01) and also higher rate of late apoptosis compared to single Erk1 and Erk2 silencing (+4.96% and +4.66%,P < 0.01). Conclusion:Our data show that liposomal siRNA-mediated down-regulation of Erk1/2 can lead to potent chemosensitizing effects in HepG2 cells. Moreover, a higher chemosensitivity following Erk2 down-regulation than Erk1 down-regulation may be associated with the higher expression of Erk2 in human HCC. [ABSTRACT FROM AUTHOR]

High-mobility group protein two (HMGA2), a nonhistone nuclear-binding protein and its downregulators; vimentin, matrix metallopeptidase-9 (MMP-9), and E-cadherin are shown to contribute to tumor progression and metastasis. Thus, in this study, we checked simultaneous delivery of HMGA-2 siRNA and the anticancer drug doxorubicin to enhance the anticancer treatment effects. For this purpose, we used MTT assay and real-time polymerase chain reaction (RT-PCR). Our results showed that dual delivery of Dox and HMGA-2 siRNA by trimethyl chitosan (TMC) significantly inhibited breast cancer cells growth. Additionally, the delivery of siRNA significantly silenced HMGA-2, vimentin, and MMP9 mRNAs, but led to overexpression of E-cadherin mRNA. [ABSTRACT FROM AUTHOR]

To concentrate a potent anticancer drug (Arteether) in tumor microenvironment, we encapsulated it in biodegradable and pH sensitive polyurethane (PU) nanomicelles (NMs). The nanocomplex was characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS). The loading capacity and release profile in pH of 5.4 and 7.4 were considered. The cytotoxicity effect was evaluatedin vitroandin vivosettings. The level of IFN-γ and IL-4 cytokines of mice splenocytes were assessed by enzyme-linked immunosorbent assay (ELISA). The nanocomplex showed negative zeta charge of −26.2 mV, size of 42.30 nm and high loading capacity (92%). Release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4. It indicated significant inhibitory effect on the growth of 4T1 cell line and increased IFN-γ level. [ABSTRACT FROM AUTHOR]

The use of chimeric antigen receptor (CAR)-modified T cells is a promising approach for cancer immunotherapy. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in T-cell activation subsequent to antigen binding. Optimal tumor removal through CAR-modified T cells requires suitable target antigen selection, co-stimulatory signaling domain, and the ability of CAR T cells to traffic, persist, and retain antitumor function after adoptive transfer. There are several elements which can improve antitumor function of CAR T cells, including signaling, conditioning chemotherapy and irradiation, tumor burden of the disease, T-cell phenotype, and supplementary cytokine usage. This review outlines four generations of CAR. The pre-clinical and clinical studies showed that this technique has a great potential for treatment of solid and hematological malignancies. The main purpose of the current review is to focus on the pre-clinical and clinical developments of CAR-based immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer is one of the most important causes of death all over the world, which has not yet been treated efficiently. Although several therapeutic approaches have been used, some side effects such as toxicity and drug resistance have been observed in patients, particularly with chemotherapy. The nanoparticle-mediated drug delivery systems (DDS) have a great potential to improve cancer treatment by transferring therapeutic factors directly to the tumor site. Such a treatment significantly decreases the adverse effects associated with cancer therapy on healthy tissues. Two main strategies, including passive and active methods, have been considered to be effective techniques which can target the drugs to the tumor sites. The current review sheds some light on the place of nanotechnology in cancer drug delivery, and introduces nanomaterials and their specific characteristics that can be used in tumor therapy. Moreover, passive and active targeting approaches focus on antibodies, particularly single chain variable fragments (scFv), as a novel and important ligand in a drug delivery system. [ABSTRACT FROM AUTHOR]

In spite of specific immune effector mechanisms raised against tumor cells, there are mechanisms employed by the tumor cells to keep them away from immune recognition and elimination; some of these mechanisms have been identified, while others are still poorly understood. Manipulation or augmentation of specific antitumor immune responses are now the preferred approaches for treatment of malignancies, and traditional therapeutic approaches are being replaced by the use of agents which potentiate immune effector mechanisms, broadly called “immunotherapy”. Cancer immunotherapy is generally classified into two main classes including active and passive methods. Interventions to augment the immune system of the patient, for example, vaccination or adjuvant therapy, actively promote antitumor effector mechanisms to improve cancer elimination. On the other hand, administration of specific monoclonal antibodies (mAbs) against different tumor antigens and adoptive transfer of genetically-modified specific T cells are currently the most rapidly developing approaches for cancer targeted therapy. In this review, we will discuss the different modalities for active and passive immunotherapy for cancer. [ABSTRACT FROM AUTHOR]