Intimin is a 94–97 kDa protein expressed on the EPEC surface that

Intimin is a 94–97 kDa protein expressed on the EPEC surface that mediates adhesion of EPEC to the epithelial gut cells [4] that mediates intimate Depsipeptide order contact with the bacterial translocated intimin receptor (Tir) [5]. The N-terminal region is conserved among the different intimin subtypes, while the C-terminal regions are highly variable.

The 29 intimin subtypes are identified according to their C-terminal amino acid sequences [6], [7] and [8]. Intimin-β is the most common subtype expressed in EPEC isolates [9], [10] and [11]. Bundle-forming pilus (BfpA) is another virulence factor, which mediates the initial contact between EPEC and the host cell Selleckchem Cyclopamine [12]. BfpA is encoded by a gene localized on a plasmid 50–70 MDa in size and is designated as EPEC adherence factor (EAF) [3], [13], [14] and [15]. Within adherent

micro-colonies of EPEC, BfpA organizes a meshwork that allows bacteria to attach to each other and to tether themselves to the host cell surface [3]. Therefore, BfpA and intimin are two important virulence factors and are considered to be strategic target candidates for the design of a new vaccine against EPEC. The generation of stable vectors expressing the desired immunogens is the goal of modern vaccine technology. The inclusion of genes encoding relevant epitopes into living, non-infective vectors that constitutively express immunological adjuvant components would be ideal. Attenuated bacteria have been used as vectors to express and deliver heterologous antigens.

This type of vaccine vector is an attractive system because it can elicit mucosal, humoral and cellular host immune responses to foreign antigens [16]. These live vectors have been used not extensively to express antigens of different types of pathogens, including viruses, bacteria and parasites, some of which have demonstrated positive results [17]. However, each vector has its unique features that should be considered before it is used. In this study, the genes encoding BfpA and intimin were investigated using two different live vectors: Mycobacterium bovis BCG Moreau (BCG) and Mycobacterium smegmatis mc2155 (Smeg) to generate the recombinant strains. C57BL/6 female mice, 4 weeks old, 18–22 g were supplied by Isogenic Mouse Breeding Facility of the Butantan Institute. All animals were cared under ethical conditions according to the Brazilian code for the use of laboratory animals [18]. All protocols were approved by the Animal Care and Ethics Committees at the Butantan Institute, São Paulo, Brazil. All cloning steps were performed in DH5-α E. coli strain grown in Luria–Bertani broth (LB) supplemented with kanamycin (20 μg/mL) or ampicillin (100 μg/mL).

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1 Many biochemical pathways associated with

hyperglycemia

1 Many biochemical pathways associated with

hyperglycemia increases generation of free radicals leading to overt oxidative stress.2 Diabetic patients have reduced anti-oxidant defenses and suffer from increased risk of free-radical mediated biomolecular damage.3 It is hypothesized therefore that supplementation of antioxidant may help reduce burden of oxidative stress and generation of oxidative stress mediated SCH727965 supplier AGEs in hyperglycemia.4 Potential health benefits of antioxidant compounds present in traditional medicinal plants arise due to their free radicals scavenging properties and inhibition of free radicals induced biomolecular including inhibition of AGEs generation and accumulation.5 The fruits and leaves of Duranta repens L. (Family. Verbenaceae) are used for treatment of malaria and abscess in Chinese traditional medicines. 6 However, enough literature is not available regarding the chemical constituents and other biological

activities in this plant. We report in this communication isolation of phytochemicals like irridoid glycoside, lignan and phenyl propanoids and evaluate their potentials for free radicals scavenging and AGEs inhibitory activities. The plant material stem and bark of Duranta repens L. (Family. Verbenaceae) were collected during the June–July 2010 from Tirumala forest, buy Gefitinib Tirupati (Andhra Pradesh, India), and identification was made by Prof. Dr. K. Madhava Chetty, Department of Cell press Botany, Sri Venkateswara University. A voucher specimen was deposited at the herbarium of Indian Institute of Chemical Technology, Hyderabad, India. The solvents used were all of AR grade were distilled under positive pressure of dry nitrogen atmosphere where necessary. Melting points were recorded on a Fisher Johns apparatus and are uncorrected. 1H and 13C spectra were measured on a Bruker 300 Hz spectrometer using tetramethylsilane as an internal standard. Mass spectra

were recorded on Agilent LC/MSD trap SL 1100 series with a 70 ev (ESI probe) and the infrared spectra on a thermo Nicolet Nexus 670 FTIR spectrometer. Visualization was performed with 5% H2SO4 solution followed by heating. Column chromatography was performed on silica gel (100–200 mesh). Thin layer chromatography (TLC) involved the use of precoated silica gel 60 F254 TLC plates of Merck. The optical rotations were measured on JASCODIP 300 digital polarimeter at 25 °C. The shade dried stem and bark of D. repens were powdered in a pulvarizer (8 kg) and extracted with methanol for 48 h followed by the concentration under reduced pressure. The resulting extract (250 g) was subjected to column chromatography over silica gel (60–120 mesh) and eluted with chloroform/methanol in the increasing order of polarity to give four fractions. Fraction I and III (1.2 g) containing the crude iridoid mixture, which were further purified by preparative HPLC on a C18 waters HR column (300 × 3.9 mm, flow rate 1.

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This review therefore provides empirical and objective evidence o

This review therefore provides empirical and objective evidence of a serious gap in this wide field of research and clinical practice. Of 148 randomised trials reporting

balance exercise interventions, none reported a validated measure of balance exercise intensity. Instead, the most common approach adopted was to describe of taxonomy of task difficulty that trial participants progressed through as they performed activities of increasing difficulty (Chin buy AZD2281 A Paw et al 2004, Chin A Paw et al 2006, Davison et al 2005,Englund et al 2005, Hauer et al 2001, Hauer et al 2002, Helbostad et al 2004, Netz et al 2007, Sjösten et al 2007, Tinetti et al 1994). One could argue that this approach is sufficient to challenge participant balance capabilities and induce an overload effect. However, this approach provides no indication of how difficult the individual performing the task found this at the time. There is an underlying

assumption that all individuals have the same balance capacity and are consistently challenged by the introduction of a ‘subsequent task’ in the hierarchy. This is analogous to a strength-training program where participants were asked to perform a leg press against resistance of 5 kg, 10 kg, and 15 kg weights in successive weeks. Although we know the resistance is increasing, we do check details not know what percentage of 1RM these weights represent for the participant. For a frail older adult this may be a very difficult activity, but for a younger, fitter individual it may not, and it would not be possible to monitor the exercise intensity level in either individual in terms of a proportion of their capability. Of the few studies that purported to report balance exercise intensity explicitly, intensity was represented inaccurately. In other words, authors used other parameters

as surrogates for intensity. Some authors reported balance exercise intensity in terms of time spent balance training. For example Silsupadol et al (2009) state that the ‘duration and intensity of this training [was] chosen based on previous studies showing that 10-hour to 12-hour balance training and 1-hour to 5-hour dual-task training programs were effective’ very (p. 382). Similarly Rubenstein et al (2000) reported an increase in balance exercise difficulty by increasing the time spent training from 5 min to 15 min over the 12 weeks of their program, and Wolf et al (2003) who report increasing the intensity of their Tai Chi intervention by increasing duration of sessions from 60 to 90 min over the course of a year. Authors also reported an increase in task difficulty as a proxy for balance exercise intensity. This was primarily done with exercise programs that progressed through standardised levels of difficulty (Davison et al 2005, Tinetti et al 1994) or with reference to task taxonomies (Helbostad et al 2004, Silsupadol et al 2006), for example Gentile’s taxonomy of movement tasks (Gentile 1987) or the task manipulations described by Geurts et al (1991).

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The relative contribution of the NH36-specific-CD4+ and CD8+ T ce

The relative contribution of the NH36-specific-CD4+ and CD8+ T cell producing cells was evaluated in an in vivo depletion assay with monoclonal antibodies ( Fig. 8). In correlation to what was detected for the specific increase of the CD4+ T cells ( Fig. 5), the TNF-α–CD4+ producing T cells ( Fig. 6), only the treatment with anti-CD4+ monoclonal antibody induced a 66% increase in the total LDU counts of mice vaccinated with CA4 saponin, indicating a main contribution of CD4+ T cells ( Fig. 8; p > 0.05) to the vaccine induced protection. On the other hand, the protective effect of the CA3-vaccine is mediated by both CD4+ and the CD8+ T cell

contributions check details since the anti-CD4+ antibody treatment induced a 43% and the anti-CD8+ antibody induced a 16% increase of the total LDU counts of CA3 vaccinated mice, respectively ( Fig. 8). This is in agreement with the increase of the percent of CD8+ NH36-specific T cells by the CA3 vaccine

( Fig. 5) and of the IFN-γ-CD4+ producing T cells ( Fig. 6). The increases in IDR, CD4–TNF-α, CD8–IFN-γ and CD8–TNF-α by the CA4 vaccine were strong correlates of protection and TGF-beta inhibitor were significantly correlated to the decrease of parasite load (p = −0.007). To confirm the relevance of TNF-α in the protection induced by C. alba we vaccinated C57BL6 wild-type and TNF-α-receptor knock-out mice and challenged them with L. chagasi amastigotes. The IDR response against Leishmania lysate was significantly increased (81%) only by the CA4 saponin vaccine in wild type

mice above their respective saline control ( Fig. 9). No increases in IDR were observed however in vaccinated TNF-α-knock-out mice ( Fig. 9). Different from what was detected in Balb/c mice treated with saline (mean = 415 LDU units) ( Fig. 7) the C57Bl6 strain was more sensitive (mean = 1200 LDU units). Confirming the role of IDR as a correlate of protection in visceral leishmaniasis, mafosfamide only the CA4-saponin vaccine (mean = 596 LDU units) induced a significant reduction of 50% of the parasite load ( Fig. 9). The TNF-α-receptor deficient mice lost the ability to clear amastigotes from the liver and showed a mean control value (2185 LDU) 56% greater than the control wild type group (1200 LDU). Protection due to the CA4 saponin was not observed in the TNF-α-receptor deficient mice. To confirm that the presence of an extra-apiose in CA4 is responsible for its increased adjuvant potential, we compared the protective efficacy of the CA3 and CA4-vaccines to the one of vaccines formulated with the CA3X and CA2 saponins of C. alba ( Fig. 1). All these saponins are naturally produced through a glycosylation series by the C. alba plant. The shorter chain is present in CA2 which has only an arabinose and a rhamnose unit attached to C-28 ( Fig. 1) and is followed by the CA3X and CA3 saponins, both with three sugars attached to the C-28 chain. The third sugar is xylose for CA3X and apiose for CA3.

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We have compared the novel ResPlex III assay and

existing

We have compared the novel ResPlex III assay and

existing techniques for the detection and subtyping of influenza virus during the influenza season 2006–2007 CB-839 [27]. The methodology must necessarily make some compromises, for example, with regard to amplification conditions during the first cycles with specific primers. Thus it is not expected that sensitivity will be the same as that of monoplex PCRs. When compared to an in-house quantitative real-time PCR for influenza virus (detection limit 1–10 TCID50/ml of a fresh influenza virus harvest), the ResPlexII v2.0 test appeared to be about 1 log10 step less sensitive. The majority of positive results obtained with the ResPlexII v2.0 test could be confirmed by other, independent conventional published, in-house qRT-PCRs or commercially available PCR methods which used other target regions of the viral genomes. This applies to all 317 influenza positive samples, 10 of 10 RSV A and B positive samples tested, 6 of 6 adenovirus positive samples, 3 of 3 bocavirus positive samples (including one questionable ResPlex result), and 13 of 14 positive coronavirus

samples (including 2 questionable ResPlex results). Differences were found for 2 parainfluenza virus 3 samples, for which ResPlex results could not be confirmed; likewise only 11 of 16 rhinovirus samples and 9 of 22 enterovirus samples tested negative in independent PCRs, but were positive with www.selleckchem.com/products/AZD2281(Olaparib).html the ResPlex method. It remains to be determined whether the observed discrepancies are weaknesses of the ResPlex system or of the other, independent PCRs. However, the manufacturer of the ResPlex method confirmed certain cross-reactivities between enteroviruses and rhinoviruses, which have conserved 5′ UTR regions that were used as

targets for the PCR primers. Since it is known that reovirus may grow in MDCK cells [9], we also screened many samples with an in-house reovirus qRT-PCR specific for mammalian orthoreovirus 1-3 (conserved region of the L3 inner capsid gene). Samples in which no other virus was detected by the ResPlex method were preferably used for the reovirus PCR. No reovirus Levetiracetam was found in 271 of the specimens for which sufficient material was still available. Whereas the specific virus growth studies summarized and discussed further above applied cell-culture adapted virus strains, the studies reported here used unadapted field virus strains and technical conditions as applied for influenza virus isolation and passaging. These studies confirmed that isolating influenza viruses in MDCK 33016PF cells effectively reduced co-infecting viruses. After only two passages and a 10−7 to 10−9 total dilution of the original specimen, adeno-, boca-, corona-, entero-, and rhinoviruses were no longer detectable. Only influenza viruses were recovered and remained the only detectable virus upon further passage.

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Currently, there are several available methods for collecting ora

Currently, there are several available methods for collecting oral fluid. However, few community-based studies have investigated which method is optimal for anti-HAV detection; important factors such as low cost, ease of collection, the validity of the results when the samples are stored under sub-optimal storage conditions, and use in a low-tech setting should be considered [15].

The aim of this study was to evaluate different oral fluid collection devices to determine which XAV939 is more suitable for distinguishing between HAV-susceptible and -protected individuals in community survey studies. The optimization panel was composed of matched serum and oral fluid samples collected from 90 health care workers without epidemiological or clinical factors associated with acute or chronic hepatitis. The health care workers were from the Oswaldo Cruz Institute and were stratified according to the total anti-HAV status of their serum. A total of 55 individuals

had documented immunity to HAV (post vaccination, n = 25; previous infection, n = 30), and 35 individuals were non-reactive for anti-HAV antibodies. The optimization panel was designed to determine the optimal salivary collection device and the most favorable parameters (dilution, incubation time and temperature) for the detection of low titers of anti-HAV antibodies in a commercial immunoassay (ImmunoComb® II HAV Ab, Orgenics, Israel) using serum samples as a reference (referred Ku-0059436 mw to as the “gold standard”). Matched serum and oral fluid samples were collected from each participant. Five milliliters (mL) of peripheral blood was drawn by venipuncture using hypodermic needles and multiple sterile vacuum blood collection tubes (Vacutainer system, Franklin Lakes, NJ, USA). Subsequently, the samples were centrifuged at 1800 × g at 25 °C for 5 min, and the sera were stored at −20 °C. Oral

fluid samples were obtained with three different commercial devices: ChemBio® (ChemBio Diagnostic Systems science Inc., NY, USA), OraSure® (originally provided as an HIV-1 Oral Specimen Collection Device) (Epitope Inc., Beaverton, USA), and Salivette® (Sarstedt, Germany). Oral fluid sample collection and processing procedures are shown in detail in Table 1. Total anti-HAV antibodies were detected with a commercially available, solid-phase enzyme immunoassay (EIA) based on the principle of immunocapture (ImmunoComb® II HAV Ab, Orgenics, Israel). The solid phase is a comb composed of 12 projections. Each projection is sensitized at two positions: an upper spot with a monoclonal anti-HAV antibody (internal control) and a lower spot with rabbit anti-human IgG and IgM antibodies.

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, 1999, Förster et al , 2005 and Cohen-Kashi Malina et al , 2009)

, 1999, Förster et al., 2005 and Cohen-Kashi Malina et al., 2009). Indeed, some are used commercially ( Culot et al., 2008 and Vandenhaute et al., 2012). A key question is the degree to which permeability data from an in vitro model reflect in vivo BBB permeability, i.e., the quality of in vitro–in vivo correlation (IVIVC). But Selleckchem LY2109761 often overlooked are the influence of the aqueous boundary layer (ABL) and variable/low-TEER

on in vitro permeability measurement. The ABL, also referred to as the unstirred water layer (UWL), is a region of poorly-stirred solution adjacent to the cell layer of interest (Korjamo et al., 2008). In vivo, the cerebral capillary network has an irregular highly branched course and a high velocity of red blood cells in the circulation ( Hudetz, 1997); even in capillaries with low or no red blood cell traffic, plasma flow has the same stirring effect ( Villringer et al., 1994). Therefore, the ABL in vivo is minimal. However, in both epithelia and endothelia in vitro, a significant ABL is present adjacent to the cell membrane as a result of inefficient stirring during

the experiment ( Barry and Diamond, 1984, Youdim et al., 2003 and Korjamo et al., 2008) ( Fig. 1). Permeation through the ABL is by passive diffusion. Hence, the ABL is a rate-limiting step for permeation of lipophilic compounds resulting in reduction of the apparent permeability ( Hidalgo et al., 1991, Karlsson and Artursson, 1991, Ruell et al., 2003, Avdeef et al., 2004, Katneni et al., 2008 and Velický et al., 2010), leading Trametinib to reduced dynamic range and lower resolution in rank-ordering compound permeation. The ABL can also be a source of bias in determining the Michaelis–Menten transport kinetic Km because of the concentration gradient created within the ABL ( Wilson and Dietschy, 1974 and Balakrishnan et al., 2007) ( Fig. 1). The ABL can also mask inhibition of specific carrier-mediated transport based on similar apparent permeability nearly measured for transporter substrate in

the absence and presence of inhibitors ( Naruhashi et al., 2003). If the ABL effect is ignored, the permeability measured in vitro will not reflect the true permeability in vivo. Currently there is no quantitative correction for ABL used routinely for in vitro BBB permeability data. An early study on the effect of ABL on in vitro BBB permeability by Ng et al. (1993) prompted awareness of the problem. Since then, most researchers have used stirring during permeability experiments to minimize the ABL effect. However, full ABL correction from analysis of in vitro permeability data is rarely used. The most common method to correct for ABL in in vitro BBB permeability data analysis is subtraction of the permeability of compounds through blank filter inserts, Pfilter (without cells) from apparent endothelial cell permeability, Papp, to obtain permeability through the cell monolayers, Pe (e.g.

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The definition of health in a given community may further define

The definition of health in a given community may further define the

enterprise of community health and how community health is put into action (e.g., Ivacaftor in vitro the methods, measures, process, and outcomes used for implementing a community health effort in a given setting). The third area – interventions – encompasses the scope of the intervention(s) being delivered within the community, and reflects the input, needs, perspectives, and goals of communities as they work to improve their health. This may include interventions such as creating safe and healthful environments; ensuring health equity for all members of the community (Centers for Disease Control, Prevention — Division of Community Health, 2013); implementing programs to promote health and to prevent disease and injury;

and fostering linkages between community and clinical programs and other resources to support health (Bauer UE et al., 2014). The final area – the “science of community health” – encompasses the methods that are SB203580 mw used by the field to develop and evaluate the evidence base that underlies the conception, design, implementation, evaluation, and dissemination of interventions. Community health draws upon a multitude of applied and theoretical public health, medical, and other scientific disciplines in terms of methods (e.g., surveillance and surveillance systems [such as the Behavioral Risk Factor Surveillance System and Youth Risk Behavioral System], epidemiology, evaluation), and expertise (e.g., prevention effectiveness, health economics, anthropology, demography, policy, health education, behavioral sciences, STK38 and law). However, the evidence base for community health may be inherently limited because of the absence of consensus, or even general agreement, on the definition and scope of a target “community”. Because of the complexity of working in communities, the “clean” scientific

methods used in experimental design often are not relevant and cannot be directly applied. Thus, one of the greatest challenges also represents an opportunity for the field of “community health” to develop innovative methods that account for the complexity of communities, variability in how health in communities is defined, and how evidence can be generated that reflects the reality of the communities in which people live, work, and play. In their assessment of what had been learned about contributions of community-based interventions to public health, Merzel and D’Afflitti suggested several other factors that help to explain the lack, or limited strong effect, of such programs, including methodological challenges to study design and evaluation, concurrent secular trends, smaller-than-expected effect sizes, limitations of the interventions, and limitations of theories used (Merzel and D’Afflitti, 2003).

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Although it is possible that behaviour change may have resulted i

Although it is possible that behaviour change may have resulted in altered environmental perceptions, such behaviour change would likely have been prompted by other factors. Our results were unchanged after adjustment for other factors shown to influence commuting decisions (Jones and Ogilvie, 2012 and Scheiner and Holz-Rau, 2013) and largely consistent with those of our analysis of baseline predictors of change (Panter et al., 2013a), suggesting that it is more likely that the changes in environmental perceptions preceded the behaviour changes. The high prevalence of walking and cycling in this sample allowed us to examine a suite of complementary metrics of changes in outcomes, but

our findings may not be generalisable to other contexts, particularly those where cycling is less prevalent. Our sample was relatively affluent and well educated and only 56% of initial participants provided Selleckchem ROCK inhibitor data at follow-up. Although baseline travel behaviour was not associated with dropout, the composition and attrition of the cohort somewhat limits the generalisability of our results. Women are overrepresented in the sample and this may have limited the precision of our estimates for men. Our outcome measures were based on changes in past-week commuting

at each time point, and may therefore have been subject to short term fluctuations rather than representing longer term patterns. We also cannot exclude the possibility of wider influences on behaviour change, such as changes in fuel prices or public selleck chemicals transport fares. Taken together with previous research, these findings confirm the potential

role of environmental interventions to promote walking and cycling, particularly those addressing the safety and pleasantness of walking and cycling routes and the convenience of public transport. These should be rigorously evaluated. The authors declare that there is no conflict of interest. The Commuting and Health in Cambridge study was developed by David Ogilvie, Simon Griffin, Andy Jones and Roger Linifanib (ABT-869) Mackett and initially funded under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Economic and Social Research Council, Medical Research Council, National Institute for Health Research and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration (grant: 087636/Z/08/Z), is gratefully acknowledged. The study is now funded by the National Institute for Health Research Public Health Research programme (project number 09/3001/06: see http://www.phr.nihr.ac.uk/funded_projects). David Ogilvie and Simon Griffin are supported by the Medical Research Council [unit programme number: MC_UU_12015/6] and Jenna Panter is supported by an NIHR post-doctoral fellowship (PDF-2012-05-157).

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, 1989) HER2 oncogene amplification was successfully measured vi

, 1989). HER2 oncogene amplification was successfully measured via quantitative reverse transcription-PCR, which demonstrated significant

increase in mRNA transcript levels in HER2-overexpressing patients compared to normal and HER2-negative patients (Savino et al., 2007). The sequence of eight amino acids in Sur2 (SWIIELLE), which is the smallest binding core of Sur2 for ESX activation domain (Asada et al., 2003), was blasted and did not match any known protein. Therefore, CHO10, which was selected as an ESX–Sur2 interaction inhibitor using our system, is likely to have selectivity over any other transcript. The inhibition of CHO10 against HER2 gene transcript via interference of the Selleck PD-1/PD-L1 inhibitor 2 ESX–Sur2 interaction was clearly attributed to the decrease in the HER2 protein. HER2 overexpression in tumors leads to constitutive activation of HER2-mediated downstream MAPK and PI3K/AKT signal cascades, as well as autocrine cell growth (Carpenter and Cohen, 1990 and Hynes and Lane, 2005). The CHO10-mediated down-regulation of the HER2 expression prevented the Tyr1221/1222 phosphorylation of HER2 and decreased the phosphorylation of MAPK and AKT with a potency similar to 10 μM canertinib treatment in SK-BR-3 cells (Fig. 1C and D). Successful

combination regimens of HER2 down-regulators have been reported; a combination of cetuximab (anti-EGFR mAb)/trastuzumab (anti-HER2 mAb) demonstrated a synergistic effect on tumor growth Osimertinib nmr inhibition in nude mice xenografted with the human pancreatic carcinoma cell lines Capan-1 and BxPC-3. This tumor inhibition was attributed to reductions of both EGFR and HER expression and AKT phosphorylation (Larbouret et al., 2012). Afatinib, an EGFR/HER2 dual TKI, efficiently inhibited the growth of cetuximab-resistant cancer cells in vitro, Sodium butyrate while elrotinib, which is an EGFR-specific TKI, showed no difference in efficacy between the cetuximab-resistant and -sensitive cells. Afatinib when combined with cetuximab in vivo, showed an additive growth inhibitory effect

in cetuximab-resistant xenografts, while no additional benefits from adding afatinib to cetuximab were observed in cetuximab-sensitive xenografts ( Quesnelle and Grandis, 2011). Other researchers have also suggested that reduction of the expression of HER2 and 611-CTF, which is a C-terminal fragmented HER2 containing intracellular and transmembrane domains, through anti-autophosphorylation at Tyr1248 of HER2/611-CTF by the EGFR/HER2 dual TKI may enhance the effect of the EGFR-targeting drug alone in cetuximab-resistant cells ( Pedersen et al., 2009; W. Xia et al., 2011). The reduction of HER2 expression when using a HER2 mRNA-antisense oligonucleotide was observed to enhance the anticancer activity of a combined doxorubicin treatment in SK-BR-3, HER2-overexpressing breast cancer cells ( Sun et al., 2011).

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