Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer tumor... more Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer tumors. In the current investigation, we exploited such a feature and utilized an anti-HER2 affibody (ZHER2:477) in combination with a pegylated liposomal doxorubicin (PLD) for concurrent passive and active targeting of HER2 overexpressing TUBO tumor, using BALB/c mice. It was determined that the affibody coupled liposomes (affisomes) was capable of increasing doxorubicin (Dox) delivery to HER2+ cells (SK-BR-3 and TUBO cells), while transferring drug similarly as low as naïve PLD to HER2- MDA-MB-231 cells. This also resulted in selectively enhance cytotoxicity. The veracity of targeting was further assessed utilizing DiD lipophilic tracer model liposomes via competition assay. An approximated 10 ligand/liposome integration caused Dox delivery at 50% of maximal delivery capacity (Kd). Such integration did not alter Dox release in vitro, while it affected the serum clearance profile. Affibody integration to PLD increased drug concentration in tumor and led to significantly further augmentation of drug in liver and spleen compared to those of PLD. Overall, such differences led to prolonging the mice life spans as compared to PLD.
Colorectal cancer (CRC) is a notable cause of cancer‑associated mortality worldwide, making it a ... more Colorectal cancer (CRC) is a notable cause of cancer‑associated mortality worldwide, making it a pertinent topic for the study of cancer and its treatment. Staphylococcal enterotoxin B (SEB), an enterotoxin produced by Staphylococcus aureus, has been demonstrated to exert anticancer and antimetastatic effects due to its ability to modify cell immunity and cellular signaling pathways. In the current study, SEB was investigated, including whether it exerts its growth inhibitory effects on colon adenocarcinoma cells. This may occur through the manipulation of a key tumor growth factor, termed transforming growth factor‑β (TGF‑β), and its signaling pathway transducer, Smad2/3. The human colon adenocarcinoma HCT116 cell line was treated with different concentrations of SEB, and cell number was measured using MTT assay at different treatment times. Smad2/3 RNA expression level was analyzed in untreated or SEB‑treated cells using quantitative polymerase chain reaction, which indicated significant differences between cell viability and Smad2/3 expression levels. SEB effectively downregulated Smad2/3 expression in the HCT116 cells at concentrations of 1 and 2 µg/ml (P=0.0021 and P=0.0017, respectively). SEB concentrations that were effective at inhibiting Smad2/3 expression were correlated with those able to inhibit the proliferation of the cancer cells. SEB inhibited Smad2/3 expression at the mRNA level in a concentration‑ and time‑dependent manner. The present study thus proposed SEB as an agent able to significantly reduce Smad2/3 expression in colon cancer cells, provoking moderate TGF‑β growth signaling and the reduction of tumor cell proliferation.
The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cis... more The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cisplatin PEGylated liposome can efficiently enhance the therapeutic effectiveness of the targeted liposome. First, Affibody molecules were incubated with Mal-PEG2000-DSPE micelle to afford formation of a maleimide-mediated thioether coupling to the COOH-terminal cysteine of Affibody. Cisplatin-loaded liposomes composed of hydrogenated soy phosphatidylcholine/ cholesterol/mPEG2000-DSPE (56.5:38.5:5 molar ratio) (150 mM) were prepared and characterized by their physicochemical properties. Affibody-conjugated micelles were then transferred into preformed liposomes by means of post insertion. The cytotoxicity and cellular uptake of Affibody-targeted (affisome) and nontargeted liposomes were tested in HER2(+) SK-BR-3, and the in vivo therapeutic activity was evaluated in TUBO breast cancer models. Anti-HER2 affisome demonstrated a higher amount of platinum intracellularly, and affected HER2(+)-SK-BR-3 cell death was at lower concentrations compared with its liposome counterparts. Further, cisplatin-affisome showed greater therapeutic efficiency than nontargeted liposome in HER2(+)-TUBO models. Equally promising, the affisome-treated mice did extend the survival of animals by several days and even left one tumor-free survivor. Affibody-targeting endowed cisplatin liposomes with significantly enhanced, albeit modest, therapeutic activity in HER2-overexpressing tumor model; however, further values are yet to be determined to advance clinical translation of these targeted nanoparticulates.
AIM: We aimed here to investigate the association between alleles and genotypes of APOE and Age-r... more AIM: We aimed here to investigate the association between alleles and genotypes of APOE and Age-related macular degeneration (AMD) development. METHODS: After ophthalmological examination, 120 patients with confirmed AMD and 120 healthy controls were enrolled in the study. The polymorphic segment of APOE gene was PCR-amplified and sequenced to determine the frequency distribution of polymorphic alleles and genotypes of this gene in the sample population. RESULTS: The frequency distribution of APOE alleles and genotypes differed significantly between the patients and the control groups (P<0.05). The frequency of APOEε2 in patients was higher than controls (P = 0.00) and this variant allele showed a significant association with AMD even after removal of the effects of age, sex and smoking by logestic regression analysis (P = 0.00, OR= 3.439; CI 95% 1.664-7.108). On the other hand, the frequency distribution of APOEε4 was not statistically different between patients and healthy cont...
Controlling the release of drugs and other therapeutic molecules has great importance in novel dr... more Controlling the release of drugs and other therapeutic molecules has great importance in novel drug delivery. Nanoparticulate systems have the ability to control drug release and increase the presence of these compounds in blood flow and could convey them to a specific position. Growth factors are endogenous peptide which begins cellular signals to regulate cellular activities. The main problem is the instability of these factors in bloodstream and lack of proper distribution in systemic administration. Nanoparticles mainly nanocarriers have the ability to overcome this problem and play a great role in intelligentization of tissue engineering because of their unique features, including the creation of physical protection and collaboration with the scaffolds and cells. Due to the increasing use of growth factors in healing damaged tissues, and their application in tissue engineering, in this article a number of nanoparticles useful for the release of growth factors with a few example...
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer tumor... more Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer tumors. In the current investigation, we exploited such a feature and utilized an anti-HER2 affibody (ZHER2:477) in combination with a pegylated liposomal doxorubicin (PLD) for concurrent passive and active targeting of HER2 overexpressing TUBO tumor, using BALB/c mice. It was determined that the affibody coupled liposomes (affisomes) was capable of increasing doxorubicin (Dox) delivery to HER2+ cells (SK-BR-3 and TUBO cells), while transferring drug similarly as low as naïve PLD to HER2- MDA-MB-231 cells. This also resulted in selectively enhance cytotoxicity. The veracity of targeting was further assessed utilizing DiD lipophilic tracer model liposomes via competition assay. An approximated 10 ligand/liposome integration caused Dox delivery at 50% of maximal delivery capacity (Kd). Such integration did not alter Dox release in vitro, while it affected the serum clearance profile. Affibody integration to PLD increased drug concentration in tumor and led to significantly further augmentation of drug in liver and spleen compared to those of PLD. Overall, such differences led to prolonging the mice life spans as compared to PLD.
Colorectal cancer (CRC) is a notable cause of cancer‑associated mortality worldwide, making it a ... more Colorectal cancer (CRC) is a notable cause of cancer‑associated mortality worldwide, making it a pertinent topic for the study of cancer and its treatment. Staphylococcal enterotoxin B (SEB), an enterotoxin produced by Staphylococcus aureus, has been demonstrated to exert anticancer and antimetastatic effects due to its ability to modify cell immunity and cellular signaling pathways. In the current study, SEB was investigated, including whether it exerts its growth inhibitory effects on colon adenocarcinoma cells. This may occur through the manipulation of a key tumor growth factor, termed transforming growth factor‑β (TGF‑β), and its signaling pathway transducer, Smad2/3. The human colon adenocarcinoma HCT116 cell line was treated with different concentrations of SEB, and cell number was measured using MTT assay at different treatment times. Smad2/3 RNA expression level was analyzed in untreated or SEB‑treated cells using quantitative polymerase chain reaction, which indicated significant differences between cell viability and Smad2/3 expression levels. SEB effectively downregulated Smad2/3 expression in the HCT116 cells at concentrations of 1 and 2 µg/ml (P=0.0021 and P=0.0017, respectively). SEB concentrations that were effective at inhibiting Smad2/3 expression were correlated with those able to inhibit the proliferation of the cancer cells. SEB inhibited Smad2/3 expression at the mRNA level in a concentration‑ and time‑dependent manner. The present study thus proposed SEB as an agent able to significantly reduce Smad2/3 expression in colon cancer cells, provoking moderate TGF‑β growth signaling and the reduction of tumor cell proliferation.
The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cis... more The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cisplatin PEGylated liposome can efficiently enhance the therapeutic effectiveness of the targeted liposome. First, Affibody molecules were incubated with Mal-PEG2000-DSPE micelle to afford formation of a maleimide-mediated thioether coupling to the COOH-terminal cysteine of Affibody. Cisplatin-loaded liposomes composed of hydrogenated soy phosphatidylcholine/ cholesterol/mPEG2000-DSPE (56.5:38.5:5 molar ratio) (150 mM) were prepared and characterized by their physicochemical properties. Affibody-conjugated micelles were then transferred into preformed liposomes by means of post insertion. The cytotoxicity and cellular uptake of Affibody-targeted (affisome) and nontargeted liposomes were tested in HER2(+) SK-BR-3, and the in vivo therapeutic activity was evaluated in TUBO breast cancer models. Anti-HER2 affisome demonstrated a higher amount of platinum intracellularly, and affected HER2(+)-SK-BR-3 cell death was at lower concentrations compared with its liposome counterparts. Further, cisplatin-affisome showed greater therapeutic efficiency than nontargeted liposome in HER2(+)-TUBO models. Equally promising, the affisome-treated mice did extend the survival of animals by several days and even left one tumor-free survivor. Affibody-targeting endowed cisplatin liposomes with significantly enhanced, albeit modest, therapeutic activity in HER2-overexpressing tumor model; however, further values are yet to be determined to advance clinical translation of these targeted nanoparticulates.
AIM: We aimed here to investigate the association between alleles and genotypes of APOE and Age-r... more AIM: We aimed here to investigate the association between alleles and genotypes of APOE and Age-related macular degeneration (AMD) development. METHODS: After ophthalmological examination, 120 patients with confirmed AMD and 120 healthy controls were enrolled in the study. The polymorphic segment of APOE gene was PCR-amplified and sequenced to determine the frequency distribution of polymorphic alleles and genotypes of this gene in the sample population. RESULTS: The frequency distribution of APOE alleles and genotypes differed significantly between the patients and the control groups (P<0.05). The frequency of APOEε2 in patients was higher than controls (P = 0.00) and this variant allele showed a significant association with AMD even after removal of the effects of age, sex and smoking by logestic regression analysis (P = 0.00, OR= 3.439; CI 95% 1.664-7.108). On the other hand, the frequency distribution of APOEε4 was not statistically different between patients and healthy cont...
Controlling the release of drugs and other therapeutic molecules has great importance in novel dr... more Controlling the release of drugs and other therapeutic molecules has great importance in novel drug delivery. Nanoparticulate systems have the ability to control drug release and increase the presence of these compounds in blood flow and could convey them to a specific position. Growth factors are endogenous peptide which begins cellular signals to regulate cellular activities. The main problem is the instability of these factors in bloodstream and lack of proper distribution in systemic administration. Nanoparticles mainly nanocarriers have the ability to overcome this problem and play a great role in intelligentization of tissue engineering because of their unique features, including the creation of physical protection and collaboration with the scaffolds and cells. Due to the increasing use of growth factors in healing damaged tissues, and their application in tissue engineering, in this article a number of nanoparticles useful for the release of growth factors with a few example...
Uploads
Papers