Due to its mild and stepwise reduction ability,

BT was ab

Due to its mild and stepwise reduction ability,

BT was able to preferentially reduce Au(3+) to Au NPs when placed in contact with an Au(3+)/Pd(2+) mixture, and subsequently, MK-2206 clinical trial the formed Au NPs served as in situ seeds for the growth of a Pd shell, resulting in the formation of Au@Pd NPs. Importantly, it is feasible to adjust the morphology of the Pd shell by varying the Pd(2+)/Au(3+) molar ratio. Au@Pd NPs with a spherical Pd shell were formed when the Pd(2+)/Au(3+) molar ratio was 1/50, while Au@Pd NPs with cubic Pd shell predominated when the ratio was increased to 2/1. The core-shell structure of synthesized Au@Pd NPs was characterized by TEM, HAADF-STEM, EDS mapping, an EDS line scan, and EDS point scan. Furthermore, density functional theory (DFT) calculations suggested that the localization of BT molecules on the surface of the Au clusters was the crucial factor for the formation of Au@Pd NPs, since the BT molecules increased the surface negative charges of the Au NPs, favoring the attraction of Pd(2+) over Au NPs and resulting in the formation of a Pd shell.”
“BackgroundAcute upper gastrointestinal (GI) hemorrhage is a common emergency department (ED) presentation whose severity ranges from benign to life-threatening and the best tool to risk stratify the disease is an upper endoscopy, either by scope or by capsule, a procedure performed almost exclusively by gastroenterologists.

Unfortunately, on-call gastroenterology specialists are often unavailable, DMXAA and emergency physicians (EPs) currently lack an alternative method to endoscopically visualize a suspected acute upper GI hemorrhage. Recent reports have shown that video capsule endoscopy is well tolerated by ED patients and has similar sensitivity and specificity to endoscopy for upper GI hemorrhage.\n\nObjectivesThe study objective was to determine if EPs can detect upper GI bleeding on capsule endoscopy after a brief

training session.\n\nMethodsA survey study was designed to demonstrate video examples of capsule endoscopy to EPs and determine if they could detect upper GI bleeding after a brief training session. All videos were generated from a prior ED-based study on patients with SNX-5422 concentration suspected acute upper GI hemorrhage. The training session consisted of less than 10minutes of background information and capsule endoscopy video examples. EPs were recruited at the American College of Emergency Physicians Scientific Assembly in Denver, Colorado, from October 8, 2012, to October 10, 2012. Inclusion criteria included being an ED resident or attending physician and the exclusion criteria included any formal endoscopy training. The authors analyzed the agreement between the EPs and expert adjudicated capsule endoscopy readings for each capsule endoscopy video. For the outcome categories of blood (fresh or coffee grounds type) or no blood detected, the sensitivity and specificity were calculated.

The present study demonstrates that emulsified halothane produces

The present study demonstrates that emulsified halothane produces reversible

QNZ nmr concentration-dependent epidural anesthesia and at 12% (v/v), emulsified halothane could produce long-term anesthesia without pathological injury.”
“Epidermal growth factor receptor (EGFR) and its most common extracellular mutant, EGFRvIII, are important therapeutic targets in multiple cancer types. A number of monoclonal antibodies and small-molecule inhibitors against these receptors are now used for anticancer treatments. New insights into the structure and function of these receptors illustrate how they can be targeted in novel ways, with expected improvements in the therapeutic efficacy. Monoclonal antibody 806 (mAb806) is an antibody that targets a conformationally exposed epitope of wild-type EGFR when it is overexpressed on tumor cells or in the presence of oncogenic mutations such as EGFRvIII. The mechanism of action of mAb806, which allows for EGFR inhibition without normal tissue toxicity, creates opportunities AMN-107 clinical trial for combination therapy and strongly suggests mAb806 will be a superior targeted delivery system for antitumor agents. Targeting

of the epitope for mAb806 also appears to be an improved strategy to inhibit tumors that express EGFRvIII. This concept of conformational epitope targeting by antibodies reflects an underlying interplay between the structure and biology of different conformational forms of the EGFR family. Cancer Res; 72(12); 2924-30. (C)2012 AACR.”
“Recent efforts have yielded a number of short peptide sequences with useful binding, sensing, and cellular uptake properties. In order to attach these

sequences to tyrosine residues on intact SB273005 concentration proteins, a three-component Mannich-type strategy is reported. Two solid phase synthetic routes were developed to access peptides up to 20 residues in length with anilines at either the N- or C-termini. In the presence of 20 mM formaldehyde, these functional groups were coupled to tyrosine residues on proteins under mild reaction conditions. The identities of the resulting bioconjugates were confirmed using mass spectrometry and immunoblot analysis. Screening experiments have demonstrated that the method is compatible with substrates containing all of the amino acids, including lysine and cysteine residues. Importantly, tyrosine residues on proteins exhibit much faster reaction rates, allowing short peptides containing this residue to be coupled without cross reactions.”
“The objective was to investigate circulating concentrations of bone formation markers (undercarboxylated osteocalcin [Glu-OC], an established marker of bone formation during fetal and early postnatal life), and Dickkopf-1 [DKK-1], a natural inhibitor of osteoblastogenesis during fetal development]) in intrauterine-growth restricted (IUGR; associated with impaired fetal skeletal development) and appropriate-for-gestational-age (AGA) pregnancies.

Traits evaluated were HCW; KPH; LM area; marbling score; fat thic

Traits evaluated were HCW; KPH; LM area; marbling score; fat thickness; dressing percentage; yield grade; retail, fat, and bone yields; and meat tenderness. Both BRD and IPD were associated with differences in yield grade in GPE7 and GPE8 steers. Animals click here treated for BRD had decreased yield grades (P = 0.003 and P = 0.02, in GPE7 and GPE8, respectively) compared with

untreated animals. Animals treated for IPD had decreased yield grades (P = 0.0006 and P = 0.004, in GPE7 and GPE8, respectively) compared with untreated animals. Incidence of BRD and IPD were associated with a reduction in fat thickness in GPE7 and GPE8 steers. Animals treated for BRD had reduced adjusted fat measurements (P = 0.0007 and P = 0.01, in GPE7 and GPE8) compared with untreated animals. Animals treated for IPD also had reduced adjusted fat measurements (P = 0.0003 and P = 0.002, in GPE7 and GPE8) compared with untreated animals. Animals treated for BRD (P < 0.007) or IPD (P < 0.02) in the GPE7 population also had decreased estimated KPH measurements compared with unaffected

animals. Animals affected with BRD in GPE8 had greater (P < 0.05) shear force measurements than unaffected animals. Animals affected with IPD in GPE8 had greater HCW (P < 0.03) and fat yield (P < 0.01) measurements but lesser bone yield (P < 0.03) and retail product yield (P < 0.01) measurements than unaffected animals. The relationship between disease and carcass traits should be given consideration by future studies that aim to develop selection strategies based on specific traits.”
“Methods. selleck kinase inhibitor Thirty-nine patients who had undergone craniotomy operations Selleck QNZ served as the basis for this study between Jul. 2007 and Dec. 2008. Standard pure-tone audiometry (PTA) and speech recognition thresholds (SRT) were calculated for all subjects before, one week and 1 year after craniotomy.\n\nResults. Statistically significant differences were not observed at the

lower and middle frequencies (0.25-2 kHz), however, differences in the hearing thresholds at higher frequencies (4-6 kHz) were statistically significant before and after craniotomy. Mean pure-tone thresholds obtained was significantly more in older subjects when compared to young patients. Moreover, the correlation between increased number of burr holes and sensorineural hearing loss (SNHL) was statistically significant.\n\nConclusions. We conclude that drill-generated noise during craniotomy has been incriminated as a cause of SNHL. Possible noise disturbance to the inner ear can only be avoided by minimizing the number of burr holes and the duration of harmful noise exposure to the cochlear structures.”
“PURPOSE To make decisions about implementing systematic depression screening, primary care physicians who serve Spanish-speaking populations need to know whether Spanish language depression-screening instruments are accurate.

Consistently, the nonphosphorylation mimicking mutant exerted low

Consistently, the nonphosphorylation mimicking mutant exerted lower tubulin deacetylase activity in vivo compared with the wild type. These data indicate that ERK/HDAC6-mediated cell

motility is through deacetylation of -tubulin. Overall, our results suggest that HDAC6-mediated cell migration could be governed by EGFR-Ras-Raf-MEK-ERK signaling.”
“Cor triatriatum is a rare congenital cardiac malformation characterized by a fibromuscular membrane that divides the left atrium into two distinct chambers. In almost all cases, it is diagnosed in childhood, whereas adult cases are extremely rare. Herein, we describe an unusual case of cor triatriatum in a 55-year-old woman who presented with embolic cerebral infarction. The patient experienced sudden-onset, transient left-sided homonymous hemianopsia and echocardiography and multidetector computed tomography GNS-1480 datasheet detected a membrane-like structure across the left atrium, confirming the diagnosis of a cor triatriatum. The laboratory examination for hypercoagulopathy was negative. She was conservatively treated with anticoagulation and her neurological manifestation gradually improved.”
“The in vitro

photoinactivation of human tumor cell lines and sheep red blood cells (SRBC) by Zinc (II) Phthalocyanine (ZnPc) was investigated using unilamellar liposome (LUV) as delivery system, in the presence and absence of cholesterol (CHOL) in the CBL0137 price formulation. The presence of CHOL improves the stability of the system showing to be essential for the photodynamic action of ZnPc. LUVs prepared without CHOL did not present any antiproliferative effects neither induced significant photohaemolysis. The presence of ZnPc in the culture medium caused total cell growth inhibition (TGI) only at concentrations higher than 250 mu mol dm(-3). For ZnPc selleck kinase inhibitor in LUV/CHOL (mass ratio = 3:1), the mean TGI values for almost all studied cells were around 80 mu mol dm(-3), and 14 mu mol dm(-3) for human ovarian carcinoma (NIH: OVCAR-3) cells. The cytoplasmic

components of OVCAR-3 and SRBC when irradiated in presence of ZnPc in LUV/CHOL were completely destroyed, culminating in cell swelling, lysis and death by necrosis. (C) 2010 Elsevier B.V. All rights reserved.”
“Coronary heart disease (CHD) is the leading cause of mortality in the industrialized world and that might also soon be the case in other parts of the world. There are several easily measured and potentially modifiable risk factors that account for a substantial proportion of the risk of CHD. The effect of risk factors interventions appears to be consistent in both genders, across different geographic regions, and by all ethnic groups, suggesting that approaches to prevention can be based on similar principles worldwide. Optimal target levels for serum cholesterol and blood pressure are not yet clear. Future risk CHD reduction will mainly be achieved by improved primary prevention.

This study aimed at estimating the prevalence of increased ABI (A

This study aimed at estimating the prevalence of increased ABI (ABI >

1.4) and to evaluate the involvement of traditional cardiovascular (CV) risk factors and the atherosclerotic burden (peripheral and carotid arteries) of these patients in a population of Southern Italy. We invited 9647 subjects, age ranging from 30 to 80, by letters to undergo an ABI measurement. Consequently, in patients with ABI > 1.4, an ultrasound evaluation of Nutlin-3 ic50 the peripheral and carotid arteries was performed. An ABI > 1.4 was found in 260 of 3412 subjects (7.6%). Statistically significant differences were reported in age, diabetes and hypertension, body mass index (BMI) and waist circumference (WC). No differences in sex distribution, dyslipidemia and smoke prevalence were observed. Moreover,

67.9% of ABI > 1.4 patients showed a peripheral intima-media thickness (IMT) > 0.9 mm; at linear regression it was correlated with ABI values; 25% of patients showed peripheral plaques. A carotid IMT > 0.9 mm was reported in 78.6% of high-ABI patients and 32.1% were affected by atherosclerotic plaques. The observed increased-ABI prevalence of 7.6% was higher than previously reported. This was more prevalent in an older population with diabetes, hypertension and obesity. Moreover, these patients are characterized check details by an extended atherosclerotic involvement. Further studies are needed to clarify this evidence, a longitudinal observation of this clinical outcome, as we are performing, could provide a number of interesting elements. (C) 2010 Published by Elsevier Ireland Ltd.”
“Background: Preadipocyte factor-1 (Pref-1) is a key regulator of adipocyte differentiation acting as

an inhibitor of adipogenesis; Pref-1 is highly expressed in embryonic tissues and placenta supporting a role in embryonic and fetal growth. The potential impact of placental Pref-1 expression in human pre- and postnatal development is unclear.\n\nObjective KU-55933 and hypotheses: To assess the contribution of placental Pref-1 to fetal and postnatal growth.\n\nPopulation and methods: Placentas (N = 99) were collected at term delivery from singleton infants, who were born either appropriate (AGA; n = 59) or small-for-gestational-age (SGA; n = 40). Auxological data of all subjects were obtained at birth. In a subset of subjects (n = 31) we also obtained weight data at 4 mo and at 1 yr, together with body composition assessment (by DXA) at the age of 1 yr. Placental expression of Pref-1 was quantified by real-time PCR; the housekeeping gene GAPDH was used for comparisons.\n\nResults: Pref-1 was significantly downregulated in the placentas from SGA babies as compared to AGA controls (P = 0.005). In SGA infants placental Pref-1 expression associated positively to body weight at 4 and 12 mo (r = 0.44, P = 0.05; r = 0.66, P = 0.

At month 12, ocular SAEs

occurred in 2 1% of patients (ou

At month 12, ocular SAEs

occurred in 2.1% of patients (out of which one patient [1.1%] experienced endophthalmitis) and 16.8% of patients experienced non-ocular SAEs. There were no deaths reported during the study.\n\nConsistent with previous studies in Caucasian and Japanese populations, EXTEND III confirms that monthly intravitreal injections of ranibizumab 0.5 mg administered over 12 months is effective and well-tolerated in South Korean www.selleckchem.com/products/tariquidar.html and Taiwanese patients with subfoveal CNV secondary to AMD.”
“Evaluation of: Rocha VZ, Chacra AP, Salgado W et al. Extensive xanthomata and severe subclinical atherosclerosis in homozygous familial hypercholesterolemia. J. Am. Coll. Cardiol. 61(21), 2193 (2013).This paper evaluation summarizes a case report of homozygous familial hypercholesterolemia. The patient in this particular case presented with gross xanthomata, elevated LDL cholesterol and extant coronary arterial

disease in early adulthood. The clinical diagnosis, physical signs and management of the condition are discussed and future treatment options for homozygous familial hypercholesterolemia are reviewed.”
“Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic

or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory AZD2171 order procedure and the expectations for the scientific content of European marketing authorization buy GSK1904529A applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency’s benefit risk assessment as basis on which to build the subsequent health technology assessment.

Specific emphasis is given to recent research on the production o

Specific emphasis is given to recent research on the production of plant-produced vaccines toward human immunodeficiency virus, malaria, tuberculosis,

hepatitis B virus, Ebola virus, human papillomavirus, rabies virus and common diarrheal diseases. Production platforms used to express vaccines in plants, including nuclear and chloroplast transformation, and the use of viral expression vectors, are described in this LY3039478 cost review. The review concludes by outlining the next steps for plant-produced vaccines to achieve their goal of providing safe, efficacious and inexpensive vaccines to the developing world.”
“Espin is a multifunctional actin-bundling protein with multiple isoforms, and has special connections to hair cell stereocilia and microvillar specializations of sensory cells in the inner ear. Fer-1 solubility dmso However, there have been no reports showing the expression and function of Espin in cancers, including melanoma. Here, it is demonstrated that Espin expression is significantly increased in melanomas that spontaneously developed in RET-transgenic mice (RET-mice). Importantly, the invasion capacity of Espin-depleted Mel-ret melanoma cells derived from a tumor of the RET-mouse was dramatically less than that of control melanoma cells with reductions of lamellipodia, focal adhesion kinase (FAK), and GTP-Rac1 activities. Correspondingly, the ratio of metastatic GKT137831 clinical trial foci in Espin-depleted

Mel-ret melanoma cells was significantly less than that of control melanoma cells in an in vivo melanoma metastasis model. Moreover, Espin could be a novel biomarker of melanoma in humans, because our immunohistochemical analysis data reveal that percentages of Espin-positive cells in human primary and metastatic melanomas were significantly higher than that of cells in melanocytic nevi. Together, these results indicate that Espin is not only a metastatic regulator for melanoma but also a potential biomarker of disease progression. (C)2013 AACR.”
“Objectives: To assess the impact of the Centers for Medicare and Medicaid Services (CMS) national coverage determination (NCD) on access for patients

with aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) in a tertiary care center. Background: TAVR has given hope to patients with AS who are deemed inoperable. The effects of the NCD on access to patients with AS has not been evaluated. Materials and Methods: A total of 94 inoperable AS patients were evaluated and treated from December 2011 through June of 2012 with TAVR. Patients who underwent transfemoral (TF) vs. non-TF access were compared. The CMS NCD was released on May 1, 2012 and on July 1, 2012, the nontransfemoral access program was put on hold due to lack of reimbursement. Results: Patients in the TF (n = 33) and non-TF access (n = 61) groups were similar in age (85.2 +/- 6.3 vs. 84.8 +/- 6.6 P = 0.

DesignPost hoc analysis of isoflavonoid exposure (mean 2

\n\nDesign\n\nPost hoc analysis of isoflavonoid exposure (mean 2.7years) during the randomized,

placebo-controlled, double-blind Women’s Isoflavone Soy Health trial.\n\nSetting\n\nGeneral community.\n\nParticipants\n\nHealthy postmenopausal women (N= 350).\n\nIntervention\n\nTwenty-five grams of isoflavone-rich soy protein (91mg of aglycone weight isoflavones: 52mg genistein, 36mg daidzein, 3mg glycitein) Apoptosis Compound Library or milk protein-matched placebo provided daily.\n\nMeasurements\n\nOvernight urine excretion, fasting plasma levels of isoflavonoids, and cognitive function measured at baseline and endpoint.\n\nResults\n\nThree hundred women (age: mean 61, range 45-92) completed both cognitive assessments and did not use hormone replacement therapy during the trial. Mean on-trial change from baseline in urine excretion of isoflavonoids was not significantly associated with change in a composite score of global cognition (P=.39). Secondary analyses indicated that change in urine excretion of isoflavonoids was inversely associated with change in a factor score representing general intelligence (P=.02) but not with factor scores representing verbal or visual episodic memory. Proteases inhibitor Mean differences

in this general intelligence factor score between women in the lowest and highest quartiles of isoflavonoid change were equivalent to an approximate 4.4-year age-associated decline. Analyses based on plasma isoflavonoid levels yielded similar but attenuated results.\n\nConclusion\n\nIn healthy postmenopausal women, long-term changes in isoflavonoids are not associated with global cognition, Adavosertib ic50 supporting clinical trial results, although greater isoflavonoid exposure from dietary supplements is associated with decrements in general intelligence but not memory; this finding requires confirmation in future studies.”
“Crude extracts from Inula aucherana, Fumaria officinalis, Crocus sativus, Vicum album, Tribulus terestris, Polygonatum multiflorum, Alkanna tinctoria and Taraxacum officinale were screened for their in vitro antioxidant and antimicrobial

properties. Total phenolic content of extracts from these plants were also determined. beta-carotene bleaching assay and Folin-Ciocalteu reagent were used to determine total antioxidant activity and total phenols of plant extracts. Antimicrobial activity was determined by using disk diffusion assay. Antioxidant activity and total phenolic content varied among plants used and Viscum album and Crocus sativus had the highest antioxidant (82.23%) and total phenolic content (42.29 mgGAE/g DW), respectively. The methanol extracts from Vicum album and Alkanna tinctoria showed antimicrobial activity against 9 out of 32 microorganisms, however extract from Inula aucherana showed antimicrobial activity against 15 out of 32 microorganisms. The results provided evidence that the studied plant might indeed be potential sources of natural antioxidant and antimicrobial agents.

We conclude that enkephalin elevations may contribute to cognitiv

We conclude that enkephalin elevations may contribute to cognitive Selleck Etomoxir impairments in hAPP mice and possibly in humans with AD. The therapeutic potential of reducing enkephalin production or signaling merits further exploration.”
“A series of substituted (benzamidostyryl) benzimidazole (3a-r) were synthesized and evaluated for their possible anti-inflammatory and ulcerogenicity. The structures of the synthesized compounds were confirmed on the basis of their spectral

data and elemental analysis. Majority of the compounds were active in carrageenan-induced hind paw edema method test and compounds 3b, 3k had shown high potency after 3 and 4 h time intervals (P < 0.001) almost equipotent to the standard drug indomethacin and showed less severity index than it.”
“Stimulating lymphocytes with

Ifn-gamma, anti-CD3, and interleukin-2 AZ 628 MAPK inhibitor promotes the proliferation of a cell population coexpressing T-lymphocyte surface antigens such as CD3, CD8a, and CD25 as well as natural killer cell markers such as NK1.1, CD49, and CD69. These cells, referred to as cytokine-induced killer cells (CIKs), display cytotoxic activity against tumour cells, even without prior antigen presentation, and offer a new cell-based approach to the treatment of malignant diseases. Because CIKs are limited in vivo, strategies to optimize in vitro culture yield are required. In the last 10 years, mesenchymal stem cells (MSCs) have gathered considerable attention. Aside from their uses in tissue engineering and as support in haematopoietic stem cell transplantations,

MSCs show notable immunomodulatory characteristics, providing further possibilities for therapeutic applications. In this study, we investigated the influence of murine MSCs on proliferation, phenotype, vitality, and cytotoxicity of murine CIKs in a coculture system. We found that CIKs in coculture proliferated within 7 days, with an average growth factor of 18.84, whereas controls grew with an average factor of 3.7 in the same period. Furthermore, higher vitality was noted in cocultured BIBF 1120 CIKs than in controls. Cell phenotype was unaffected by coculture with MSCs and, notably, coculture did not impact cytotoxicity against the tumour cells analysed. The findings suggest that cell-cell contact is primarily responsible for these effects. Humoral interactions play only a minor role. Furthermore, no phenotypical MSCs were detected after coculture for 4 h, suggesting the occurrence of immune reactions between CIKs and MSCs. Further investigations with DiD-labelled MSCs revealed that the observed disappearance of MSCs appears not to be due to differentiation processes.”
“Objective: To evaluate the association between mucin 2 (MUC2) expression and clinicopathological characters of colorectal cancer.\n\nMethods: A literature search was performed on December 31, 2010 according to defined selection criteria.

A strong acid phosphatase reaction was evident in the endothelium

A strong acid phosphatase reaction was evident in the endothelium. BPB reaction for protein was moderate to intense. Ducts and acini were PAS and Alcian Blue reactive. The reaction for glycogen and AMPS contents in the gland increased with age. It was very intense in the pubertal animals. Moderate DNA activity, mild to moderate alkaline and acid phosphatases in the glandular acini and ductal epithelium revealed functionally active secretory glands particularly in the pubertal animals.”
“The broad-spectrum antitumor agent 5-fluorouracil (5-FU), has been used to treat various solid malignant tumors. However, its short life-time in vivo and poor ability to cross the Staurosporine molecular weight blood-brain

barrier has limited its application to brain tumor therapy. In order to develop a 5-FU derivative that localizes efficiently to the brain while retaining potent antitumor activity, we conjugated 5-FU with N,N-dimethylethylenediamine via an amide bond. The stability of the resulting 5-FU derivative (D-FU) was tested in vitro in phosphate buffer, rat plasma and brain homogenate. The pharmacokinetic and biodistribution studies in brains of the rats showed a higher C-max (the maximal concentration) and an increased AUC(0-t) (the area under the concentration-time curve) which was 6-fold that of 5-FU. In addition, compared to 5-FU, D-FU exhibited lower toxicity in an acute toxicity

assay and similar antitumor activity in the C6 cell line. In conclusion, D-FU has the potential to be developed into an efficient brain Sapitinib in vitro delivery drug.”
“Experimental tumor vaccination and adoptive T-cell AZD8931 Protein Tyrosine Kinase inhibitor therapies show that interferon-gamma (IFN-gamma)-producing CD4(+) T helper cells (Th1) can be highly effective in tumor prevention and therapy. Unexpectedly, first vaccine trials in humans revealed that tumor immune therapy may not only be protective, but, on the contrary, even promote tumor progression. Here, we analyzed T-cell immune responses to the epithelial cell adhesion molecule (EpCAM), one of the most common tumor-associated antigens (TAA) serving

as immune target in colon cancer patients. Th-cell priming against EpCAM inevitably resulted in interleukin-4 (IL-4)-dominated Th2 responses, even under most stringent Th1-inducing conditions. These EpCAM-reactive Th2 cells rather promoted growth of EpCAM-expressing tumors. To analyze the role of IL-4 in tumor immune evasion, we generated EpCAM-reactive Th1 cells from IL-4.ko mice. These Th1 cells provided tumor-specific protection and established highly protective Th1 memory responses, even in naive BALB/c mice. Inhibition of tumor growth by Th1 cells resulted in intratumoral expression of cytokines of the IL-12 family and of IFN-gamma. Preventing activation-associated death of Th1 cells further increased intratumoral IFN-gamma expression and improved therapeutic efficacy. Thus, human TAA may promote tumor immune evasion by strongly favoring Th2 development. (Blood.