• Biomolecules & Therapeutics
• /
• 제19권3호
• /
• pp.331-335
• /
• 2011

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권8호
• /
• pp.4717-4721
• /
• 2013

Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. Forty eight HNSCC patients were selected between 2006 and 2009 diagnosed at the Royal Darwin Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with negative surgical margins with hematoxylin and eosin (HandE) were chosedn for further analysis. A total of 77 surgical margins were obtained and subsequently analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal eIF4E antibodies. Contingency table and ${\chi}^2$-test were used to investigate the correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival of the HNSCC patients. The follow up period was 74 months (range 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.

• 대한병리학회지
• /
• 제52권6호
• /
• pp.386-395
• /
• 2018

Background: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p=.003) and distant metastasis (p=.001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p<.001), but not for recurrence-free survival (p=.151). Conclusions: Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

• 약학회지
• /
• 제46권6호
• /
• pp.459-465
• /
• 2002

$\beta$-l, 3-glucans are well known to enhance the immune reactions, resulting in antitumor, antibacterial, antiviral, anticoagulatory and wound healing activities. $\beta$-1, 3-glucans have various activities depending on molecular weight, degree of branching, conformation, water-solubility and intermolecular association. However, the $\beta$-1, 3-glucans linked backbone structure is essential and $\beta$-D-glucopyranosyl units are required for immunopotentiating activities. In this study, we tested the immunophamacological activities of insoluble $\beta$-1, 3-glucan from Agrobacterium sp. R259 KCTC 10197BP and confirmed the following activities: (1) IFN-${\gamma}$ production in PBMCs in the presence or in the absence of PHA, LPS, IL-18, and IL-12; (2) the induction of various cytokines in the spleen and thymus; (3) the adjuvant effect on the antibody production; (4) the cytotoxic and antitumor effects on cell lines and ICR mice. These results strongly suggest that $\beta$-1, 3-glucan from Agrobacterium sp. R259 KCTC 10197BP possesses various immunopharmacologica1 activities.

• Nuclear Medicine and Molecular Imaging
• /
• 제40권1호
• /
• pp.48-50
• /
• 2006

A 38-year-old female with arthralgia in right elbow joint for 6 months was referred for a bone scan which showed diffuse uptakes of $^{99m}Tc$-MDP in the liver and spleen without hepatosplenomegaly. She had a history of hepatitis B vaccination 3 days ago. These uptakes were disappeared on the follow-up bone scan after 4 months. We suggest this transient diffuse hepatic uptake after vaccination of hepatitis B might be due to aluminum component within the hepatitis B vaccine as adjuvant.

• Molecular & Cellular Toxicology
• /
• 제1권1호
• /
• pp.40-45
• /
• 2005

Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.

• BMB Reports
• /
• 제38권6호
• /
• pp.717-724
• /
• 2005

The nontoxic B subunit of cholera toxin (CTB) can significantly increase the ability of proteins to induce immunological tolerance after oral administration, when it was conjugated to various proteins. Recombinant CTB offers great potential for treatment of autoimmune disease. Here we firstly investigated the feasibility of silkworm baculovirus expression vector system for the cost-effective production of CTB under the control of a strong polyhedrin promoter. Higher expression was achieved via introducing the partial non-coding and coding sequences (ATAAAT and ATGCCGAAT) of polyhedrin to the 5' end of the native CTB gene, with the maximal accumulation being approximately 54.4 mg/L of hemolymph. The silkworm bioreactor produced this protein vaccine as the glycoslated pentameric form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB. Further studies revealed that mixing with silkworm-derived CTB increases the tolerogenic potential of insulin. In the nonconjugated form, an insulin : CTB ratio of 100 : 1 was optimal for the prominent reduction in pancreatic islet inflammation. The data presented here demonstrate that the silkworm bioreactor is an ideal production and delivery system for an oral protein vaccine designed to develop immunological tolerance against autoimmune diabetes and CTB functions as an effective mucosal adjuvant for oral tolerance induction.

• BMB Reports
• /
• 제30권5호
• /
• pp.346-351
• /
• 1997

The maximum adsorption/desorption conditions and the adsorption mechanism of globular proteins to vaccine adjuvants were determined. The maximum adsorption ratio of protein to the $Al^{3+}$ content of aluminum oxyhydroxide and the optimal adsorption pH are 2:1 (${\mu}g:{\mu}g$) for bovine serum albumin (BSA) at pH 6.0 and 2.5:1 (${\mu}g:{\mu}g$) for immunoglobulin G (IgG) at pH 7.0, respectively. The maximum adsorption ratio onto aluminum phosphate gel was 1.5:1 (${\mu}g$ Protein:${\mu}g$ $Al^{3+}$) at pH 5.0 for both BSA and IgG. Adsorption of the native globular proteins, BSA and IgG, to aluminum oxyhydroxide and aluminum phosphate gel was reversible as a function of pH. Complete desorption of these proteins from aluminum phosphate gel was observed at alkaline pH, whereas only 80~90% removal from aluminum oxyhydroxide was achieved with alkaline pH and 50 mM phosphate buffer. We conclude that electrostatic and hydrogen bonding interactions between the native proteins and adjuvants are important binding mechanisms for adsorption, and that the surface charge of the protein and the colloid components control the maximum adsorption conditions.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권12호
• /
• pp.4759-4763
• /
• 2014

Radiation therapy in ovarian cancers has been considered an outdated concept for many years, mainly due to its toxicity and failure to show benefit in terms of survival. Chemotherapy has been extensively used after surgery for these cancers and it has almost replaced radiation therapy as an adjuvant treatment. Nevertheless, failures in ovarian cancers continue to occur even with the use of newer and effective chemotherapy regimens. About 70% patients demonstrate recurrence in the abdomen or pelvis after first line chemotherapy in ovarian cancers. With advances in technology and sophistication of radiation techniques, along with the molecular and biological knowledge of distinct histological subtypes, there is a need to redefine the role of radiation therapy. This review article focuses on the literature on use of radiation in ovarian cancers and its rationale and indications in the present day. For this, a literature pub med/medline search was performed from January 1975 to March 2014 to redefine the role of radiotherapy in ovarian cancers.

• 대한의생명과학회지
• /
• 제23권3호
• /
• pp.175-184
• /
• 2017

Cholera toxin (CT) is an ADP-ribosylating bacterial exotoxin that has been used as an adjuvant in animal studies of oral immunization. The mechanisms of mucosal immunogenicity and adjuvanticity of CT remain to be established. In this study, we investigated the role of indoleamine 2,3-dioxygenase (IDO), which participates in the induction of immune tolerance, in CT-mediated breakdown of oral tolerance. When IDO-deficient ($IDO^{-/-}$) mice and their littermates were given oral ovalbumin, significant changes in antibody responses, footpad swelling and $CD4^+$ T cell proliferation were not observed in $IDO^{-/-}$ mice. Feeding of CT decreased IDO expression in mesenteric lymph nodes (MLN) and Peyer's patch (PP). CT-induced downregulation of IDO expression was reversed by inhibitors of nuclear factor-kappa B (NF-${\kappa}B$), pyrrolidine dithiocarbamate and p50 small interfering RNA. IDO expression was downregulated by the NF-${\kappa}B$ inducers lipopolysaccharide and tumor necrosis factor-${\alpha}$. CT dampened IDO activity and mRNA expression in dendritic cells from MLN and PP. These data indicate that CT disrupts oral tolerance by activating NF-${\kappa}B$, which in turn downregulates IDO expression. This study betters the understanding of the molecular mechanism underlying CT-mediated abrogation of oral tolerance.