Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.
Youn Seon Min;Oh Young Kee;Kim Joo Heon;Park Mi Ja;Seong In Ock;Kang Kimun;Chai Gyuyong
Radiation Oncology Journal
/
v.23
no.1
/
pp.51-60
/
2005
Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.
A beeswax-treated paper has no air permeability but has the water repellency compared with a general Hanji. Because of these properties, the differences of the aging factors and mechanisms between the outer partition of beeswax-treated paper that is affected by the surrounding conservation environment and the inner partition of it that is not affected are bigger than general books. In this research, we analyzed and compared the aging characteristics through the accelerated aging of the beeswax-treated paper by some air and humidity conditions. The results of the physical and optical analysis after the artificial aging, it was shown that the oxygen accelerates the aging of the beeswax-treated paper and the condition with the humidity 50% RH is more stable than the condition with the humidity 0% RH. The results of the CG/MS analysis that was conducted to figure out the decomposition charateristics of the beeswax according to the air quality and the humidity, a low molecular weight compound that the number of carbon is C9-C20 including a fatty acid such as a palmitic acid was increased as the aging was progressed. However, under the same environment, a compound that the number of carbon is C21-C36 including a hydrocarbon and a aliphatic alcohol and a high molecular weight compound that the number of carbon is more than C34 including a wax ester were decreased. A rate of change according to the air quality and the humidity was similar to the beeswax-treated papers.
A post-irradiation annealing study was conducted with use of reactor pressure vessel(RPV) steel A533B Cl.1 base metal irradiated to a dose of 4.84$\times$10$^{18}$ n/$\textrm{cm}^2$ at about 38$0^{\circ}C$. Microhardness and positron annihilation (PA) methods were used to obtain better understanding of the recovery of radiation hardening. Isochronal anneal experiments indicated that two recovery processes occur during annealing of irradiated specimens. The first recovery process occurs in the temperature range of 280-3O5$^{\circ}C$, Michrohardness and positron annihilation (PA) methods were used to obtain better understanding of the recovery of radiation hardening. Isochronal anneal experiments indicated that two recovery processes occur during annealing of irradiated specimens. The first recovery process occurrs in the temperature range of 280-305$^{\circ}C$. The variations of Ip, Iw and R parameters indicated that the formation of vacancy clusters by vacancy agglomeration and the annihilation of monovacancies are the first recovery process. The second recovery process occurs in the range of 405-49$0^{\circ}C$ and positron annihilation parameters measured indicated that the dissolution of carbon atoms decorated around vacancy-type defects and possible precipitates, and the annihilation of monovacancies give rise to the second recovery process. It was further indicated that radiation anneal hardening (RAH) in the range of 305-405$^{\circ}C$ between the temperature ranges for the two processes occurs due to the formation of carbon-decorated vacancy clusters and precipitates. The activation energies, orders of reaction and other characteristics of recovery processes were determined by the Meechan-Brinkman method. The activation energy for the first recovery process was determined as 1.76 eV and that for the second recovery process as 2.00eV. These values are lower than those obtained by other workers. This difference may be attributed to the lower copper content of the RPV steel used in the present study. The order of reaction for the first recovery process was determined as 1.78, while that for the second recovery process as 1.67 Non-integer orders of reaction for recovery processes seem to be attributed to the fact that several mechanisms for the first order and the second order of reaction are compounded in one process. This result also supports for the above conclusions from measurements of PA parameters.
The purpose of this study is to provide the basic data such as distribution status, growth characteristics, and the structural characteristics of forest stands for the systematic conservation and management of relict forest trees (stem girth of 300cm or larger) established naturally in Gangwon Province, Korea. The survey showed that 434 individuals of 19 species (conifers: 228 individuals of 4 species, broad-leaved trees: 206 individuals of 15 species) were distributed in Gangwon Province, and Taxus cuspidata was the most abundant among them with 203 individuals or about 46.7 % of the total. The stem girth was average of 404cm (conifers: 373cm, broad-leaves: 421cm), and Tilia amurensis with multi-stemmed growing on Sorak mountain range had the largest stem girth at 1,113cm. The average height and the crown width of relict forest trees were 15.4m and 10.0m, respectively. Although the environments of relict forest trees showed a slight difference by species, the relative appearance frequencies of most trees were high in the environments where the altitude was higher than 1,000 m, slope degree was greater than $25^{\circ}$, the slope faced north, and microtopography was at the upper of slopes. Regarding the stand characteristics of relict forest trees per unit area ($/100m^2$), the average total coverage was 294% (max. 475%), the total average number of species was 36 species (max. 60 species), the average species diversity index (H') was 2.560 (max. 3.593), the average canopy closure was 84.8% (max. 94.6%), and the average basal area (/ha) was $52.7m^2$ (max. $116.4m^2$, relict trees $30.0m^2$, and other trees $22.7m^2$). The analysis of the dynamics of the forest stands where relict forest trees were growing showed four types of the maintenance mechanisms of relict forest trees depending on the supply pattern of succeeding trees: "Low-density but persistent type (Quercus mongolica, Abies holophylla, Tilia amurensis, and Pyrus ussuriensis)," "Long ago stopped type (Pinus densiflora)," "Recently stopped type (Abies nephrolepis, Quercus variabilis, and Betula schmidtii)," and "Periodically repeated types of supply and stop (Salix caprea and Quercus serrata).".
Halitosis is a generally accepted marker of diseases in the oral cavity and of systemic and gastrointestinal disorders. Based on these authors' previous findings (that (1) there is a close association between H. pylori infection and halitosis; (2) Korea red ginseng may suppress the colonization of H. pylori, fight H. pylori-induced cytotoxicity, and impose significant anti-inflammatory actions in patients with chronic gastritis; and (3) H. pylori infection is linked with the generation of significant levels of volatile sulfur compounds (VSCs), and the levels of VSCs correlate significantly with H. pylori-associated mucosal damages), in the current study, the authors documented the molecular mechanisms of Korea red ginseng's efficacy in ameliorating halitosis. When the RAW 264.7 cells were treated with the $H_2S$ releasing compound NaHS, the mRNA expression of cystathionine ${\gamma}$-lyase (CSE), IL-6, COX-2, and iNOS were more significantly induced compared with the vehicle-treated group. The cytoskeletal components of ezrin's and moesin's mRNA expressions were elevated by NaHS treatment accompanied by the activation of MAPK, p38, and ERK. Korea red ginseng pretreatment reduced both the NaHS-induced CSE expression and the proinflammatory genes (e.g., IL-6, COX-2, and iNOS) in a concentration-dependent manner. The ERM expression and the phosphorylation of p38 were also significantly reduced by Korea-red-ginseng pretreatment. Overall, Korea red ginseng pretreatment imposed significant anti-inflammatory effects through the downregulation of the NaHS-triggered proinflammatory gene expression, CSE, and ERM mRNA expression. Korea red ginseng could thus be said to be a key remedy of halitosis and to be effective in relieving gastric inflammation.
In the current study, the mesenchymal stem cells (MSCs) isolated and propagated from the human umbilical cord blood (UCB) were tested for their capabilities of differentiation into chondrocytes in vitro. The mesenchymal progenitor cells (MPCs) collected from UCB were cultured in a low glucose DMEM medium with 10% FBS, L-glutamine and antibiotics. The human MSC colonies were positively stained by PAS reaction. When the immunophenotypes of surface antigens on the MSCs were analyzed by fluorescence-activated cell sorter (FACS) analysis, these cells expressed positively MSC-related antigens of CD 29, CD44, CD 90 and CD105, whereas they did not express antigens of CD14, CD31, CD34, CD45, CD133 and HLA-DR. Following induction these MSCs into chondrocytes in the chondrogenic differentiation medium for 3 weeks or more, the cells were stained positively with safranin O. We clearly confirmed that human MSCs were successfully differentiated into chondrocytes by RT-PCR and immunofluorescent stain of type-II collagen protein. These data also indicate that the isolation, proliferation and differentiation of the hUCB-derived MSCs in vitro can be used for elucidating the mechanisms involved in chondrogenesis. Moreover this differentiation technique can be applied to developing cell-based tissue regeneration or repair damaged tissues.
In this study, we evaluated the antidiabetic effect of a submerged culture of Ceriporia lacerata mycelium (CL01) on hematological indices, as well as protein and mRNA expression of the insulin-signaling pathway, in db/db mice. After CL01 was administrated for 4 weeks, blood glucose levels decreased consistently, and plasma insulin and c-peptide levels each decreased by roughly 55.8%, 40% of those in the negative control (p<0.05). With regard to HOMA-IR, an insulin resistance index, insulin resistance of the CL01-fed group improved over that of the negative control group by about 62% (p<0.05). In addition, we demonstrated that the protein expression levels of pIR, pAkt, pAMPK, and GLUT4 and the mRNA expression levels of Akt2, IRS1, and GLUT4 in the muscle cells of db/db mice increased in the CL01-fed group compared to the corresponding levels in the control group. These results demonstrate that CL01 affects glucose metabolism, upregulates protein and gene expression in the insulin-signaling pathway, and decreases blood glucose levels effectively by improving insulin sensitivity. More than 90% of those who suffer from type 2 diabetes are more likely to suffer from hyperinsulinemia, hypertension, obesity, and other comorbidities because of insulin resistance. Therefore, it is possible that CL01 intake could be used as a fundamental treatment for type 2 diabetes by lowering insulin resistance, and these results may prove be useful as basic evidence for further research into the mechanisms of a cure for type 2 diabetes.
The use of calcite-forming bacteria (CFB) in crack remediation and durability improvements in construction materials creates a permanent and environmentally-friendly material. Therefore, research into this type of application is stimulating interdisciplinary studies between microbiology and architectural engineering. However, the mechanisms giving rise to these materials are dependent on calcite precipitation by the metabolism of the CFB, which raises concerns about possible hazards to cement-based construction due to microbial metabolic acid production. The aim of this study was to determine target microorganisms that possibly can have bio-corrosive effects on cement mortar and to assess multi-functional CFBs for their safe application to cement structures. The chalky test was first used to evaluate the $CaCO_3$ solubilization feature of construction sites by fungi, yeast, bacterial strains. Not all bacterial strains are able to solubilize $CaCO_3$, but C. sphaerospermum KNUC253 or P. prolifica KNUC263 showed $CaCO_3$ solubilization activity. Therefore, these two strains were identified as target microorganisms that require control in cement structures. The registered patented strains Bacillus aryabhatti KNUC205, Arthrobacter nicotianae KNUC2100, B. thuringiensis KNUC2103 and Stenotrophomonas maltophilia KNUC2106, reported as multifunctional CFB (fungal growth inhibition, crack remediation, and water permeability reduction of cement surfaces) and isolated from Dokdo or construction site were unable to solubilize $CaCO_3$. Notably, B. aryabhatti KNUC205 and A. nicotianae KNUC2100 could not hydrolyze cellulose or protein, which can be the major constituent macromolecules of internal materials for buildings. These results show that several reported multi-functional CFB can be applied to cement structures or diverse building environments without corrosive or bio-deteriorative risks.
Radiotherapy is commonly used in treating many kinds of cancers which cannot be cured by other therapeutic strategies. However, radiotherapy also induces the damages on the normal tissues. Radiation-induced fibrosis is frequently observed in the patients undergoing radiotherapy, and becomes a major obstacle in the treatment of intrahepatic cancer. Hedgehog (Hh) that is an essential in the liver formation during embryogenesis is not detected in the healthy liver, but activated and modulates the repair process in damaged livers in adult. The expression of Hh increases with the degree of liver damage, regulating the proliferation of hepatic progenitors and hepatic stellate cells (HSC). In addition, Hh induces epithelial-to-mesencymal transition (EMT) and activation of myofibroblasts. In the irradiated livers, up-regulated expression of Hh signaling was associated with proliferation of progenitors, EMT induction, and increased fibrosis. Female-specific expression of Hh leaded to the expansion of progenitors and the accumulation of collagen in the irradiated livers of female mice, indicating that gender disparity in Hh expression may be related with radiation-susceptibility in female. Hence, Hh signaling becomes a novel object of studies for fibrogenesis induced by radiation. However, the absence of the established experimental animal models showing the similar physiopathology with human liver diseases and fibrosis-favorable microenvironment hamper the studies for the radiation-induced fibrosis, providing a few descriptive results. Therefore, further research on the association of Hh with radiation-induced fibrosis can identify the cell and tissue-specific effects of Hh and provides the basic knowledge for underlying mechanisms, contributing to developing therapies for preventing the radiation-induced fibrosis.
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