Current Issue : January - March Volume : 2017 Issue Number : 1 Articles : 6 Articles
Background: Atopic dermatitis (AD) is characterized by chronic inflammation of the skin. AD develops\nmainly in infants and young children. It induces skin disorders and signals the initiation of the allergic march\nincluding allergic asthma and rhinitis. Probiotics modify intestinal microbial populations in a beneficial way\nfor human and animal hosts by reducing inflammatory cytokines.\nObjective: As a result of their immunomodulatory properties, probiotics have been considered a promising\ntherapeutic option for the prevention and treatment of AD.\nDesign: In this study, we examined the effects of GI7, a potential probiotic mixture consisting of seven strains\nof bifidobacteria and lactic acid bacteria, on AD in a mouse model.\nResults: Administration of GI7 for 8 weeks reduced AD-like skin lesions and induced changes in the levels of\nserum markers such as immunoglobulin E and cytokines related to T helper (Th)1 and Th2 cells, and in skin\nbarrier genes. Alleviation of AD seems to be associated with GI7-induced generation of CD4Foxp3\nregulatory T cells.\nConclusions: The probiotic mixture may have potential to improve symptoms of AD....
Background: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the\npatients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients\nwith metastatic colorectal cancer is approximately 22ââ?¬â??24 months. Some immunotherapeutic approaches had\nbeen attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach\nhas shown a novel direction for colon cancer prevention and therapy.\nMethods: In this study, the experiments were designed including prevention and therapeutic stages in order to attain\neffect against tumor recurrence in clinical settings. The anti-tumor efficacy of a novel cytokine adjuvant vaccine that\ncontained cytokines GM-CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse\ntumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the\nexpression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow\ncytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and\nthe lactic dehydrogenates (LDH) release assays. IFN-Ã?³, IL-2 and GM-CSF secretion in serum was assayed by ELISA.\nResults: Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended\nthe survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were\nsignificantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells\nplay a key role in anti-tumor response.\nConclusions: The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response\nand represented a promising immunotherapeutic approach for patients with colon cancer....
Background: Glioblastomas (GBMs) are highly malignant brain tumours with a poor prognosis, and current\ncytotoxic regimens provide only a limited survival benefit. The PI3K/Akt/mTOR pathway has been an attractive\ntarget for therapy due to its high activation in GBMs as well as other cancers. The dual pan-PI3K/mTOR kinase\ninhibitor dactolisib (NVP-BEZ235) is an anti-neoplastic compound currently under investigation. However, little\nis known about its efficacy in human GBMs. We aimed at evaluating the efficacy of dactolisib in human\nglioblastoma cells, as well as in murine models carrying human GBM xenografts.\nMethods: To assess the effect of dactolisib in vitro, MTS assay, manual cell count, BrdU incorporation and Annexin V\nstaining experiments were used to observe growth and apoptosis. Furthermore, Akt phosphorylation (S473), a\ndownstream target of PI3K, was explored by western blotting. Animal studies utilizing orthotopic xenograft models of\nglioblastoma were performed in nude rats and NOD/SCID mice to monitor survival benefit or inhibition of tumor growth.\nResults: We found that dactolisib in vitro shows excellent dose dependent anti-growth properties and\nincrease in apoptosis. Moreover, dose dependent inhibition of Akt phosphorylation (S473), a downstream\neffect of PI3K, was observed by western blotting. However, in two independent animal studies utilizing nude\nrats and NOD/SCID mice in orthotopic xenograft models of glioblastoma, we observed no survival benefit or\ninhibition of tumour growth. Severe side effects were observed, such as elevated levels of blood glucose and\nthe liver enzyme alanine transaminase (ALT), in addition to diarrhoea, hair loss (alopecia), skin rash and\naccumulation of saliva in the oral cavity.\nConclusion: Taken together, our results suggest that despite the anti-neoplastic efficacy of dactolisib in\nglioma treatment in vitro, its utility in vivo is questionable due to toxicity....
Present study was planned to evaluate cytotoxicity of methanolic extract of E. hirta against NCIH-522 and Vero cell line. Fourier transform infrared spectroscopy (FTIR) analysis of the methanolic extract of E. hirta was performed. 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used to performed cytotoxicity study of methanolic extract of E. hirta. Doxorubicin was considered as standard reference drug. Concentrations 1000-0.05 µg/ml of extract and doxorubicin were used in study. FTIR spectrum of methanolic extract of E. hirta was showed seven peaks/centers, viz., 674.541, 1050.082, 1096.320, 1285.406, 1389.313, 1559.797 and 2939.877 at the wavelength region of 4,000.00–650.00 cm−1. The results of present study revealed that 50% cell growth inhibition (IC50) of methanolic extract of E. hirta and doxorubicin was 466.13 µg/ml and 531.14 µg/ml against NCIH-522 cell line and 1375.22 µg/ml and 2392.71 µg/ml against Vero cell line respectively. Methanolic extract was found to be toxic against NCIH-522 and Vero cell line. It is due to the presence of toxic class of phytocompounds demonstrated in FTIR spectrum. Further, there is need to isolate, identify and confirm these toxic phytocompounds from the extract....
Background: Circulating tumor cells (CTCs) have shown prognostic relevance in many cancer types. However, the\nmajority of current CTC capture methods rely on positive selection techniques that require a priori knowledge\nabout the surface protein expression of disseminated CTCs, which are known to be a dynamic population.\nMethods: We developed a microfluidic CTC capture chip that incorporated a nanoroughened glass substrate for\ncapturing CTCs from blood samples. Our CTC capture chip utilized the differential adhesion preference of cancer\ncells to nanoroughened etched glass surfaces as compared to normal blood cells and thus did not depend on\nthe physical size or surface protein expression of CTCs.\nResults: The microfluidic CTC capture chip was able to achieve a superior capture yield for both epithelial cell\nadhesion molecule positive (EpCAM+) and EpCAM- cancer cells in blood samples. Additionally, the microfluidic\nCTC chip captured CTCs undergoing transforming growth factor beta-induced epithelial-to-mesenchymal\ntransition (TGF-�²-induced EMT) with dynamically down-regulated EpCAM expression. In a mouse model of\nhuman breast cancer using EpCAM positive and negative cell lines, the number of CTCs captured correlated\npositively with the size of the primary tumor and was independent of their EpCAM expression. Furthermore,\nin a syngeneic mouse model of lung cancer using cell lines with differential metastasis capability, CTCs were\ncaptured from all mice with detectable primary tumors independent of the cell linesâ�� metastatic ability.\nConclusions: The microfluidic CTC capture chip using a novel nanoroughened glass substrate is broadly applicable to\ncapturing heterogeneous CTC populations of clinical interest independent of their surface marker expression and\nmetastatic propensity. We were able to capture CTCs from a non-metastatic lung cancer model, demonstrating\nthe potential of the chip to collect the entirety of CTC populations including subgroups of distinct biological and\nphenotypical properties. Further exploration of the biological potential of metastatic and presumably non-metastatic\nCTCs captured using the microfluidic chip will yield insights into their relevant differences and their effects on tumor\nprogression and cancer outcomes....
Background: NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific\ntransporters, OCT1 and OCT3. We sought to determine the anti-tumorigenic effects of NT1014 in human ovarian\ncancer cell lines as well as in a genetically engineered mouse model of high-grade serous ovarian cancer.\nMethods: The effects of NT1014 and metformin on cell proliferation were assessed by MTT assay using the human\novarian cancer cell lines, SKOV3 and IGROV1, as well as in primary cultures. In addition, the impact of NT1014 on\ncell cycle progression, apoptosis, cellular stress, adhesion, invasion, glycolysis, and AMPK activation/mTOR pathway\ninhibition was also explored. The effects of NT1014 treatment in vivo was evaluated using the K18 âË?â?? gT121+/âË?â??; p53fl/\nfl; Brca1fl/fl (KpB) mouse model of high-grade serous ovarian cancer.\nResults: NT1014 significantly inhibited cell proliferation in both ovarian cancer cell lines as well as in primary\ncultures. In addition, NT1014 activated AMPK, inhibited downstream targets of the mTOR pathway, induced G1 cell\ncycle arrest/apoptosis/cellular stress, altered glycolysis, and reduced invasion/adhesion. Similar to its antitumorigenic\neffects in vitro, NT1014 decreased ovarian cancer growth in the KpB mouse model of ovarian cancer.\nNT1014 appeared to be more potent than metformin in both our in vitro and in vivo studies.\nConclusions: NT1014 inhibited ovarian cancer cell growth in vitro and in vivo, with greater efficacy than the\ntraditional biguanide, metformin. These results support further development of NT1014 as a useful therapeutic\napproach for the treatment of ovarian cancer....
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