These technical complications

These technical complications Selleckchem A1331852 influenced posttransplant observations. Renal artery thrombosis resulted in anuria and increased serum creatinine levels. A stenotic renal vein was associated with a greater peak of serum creatinine. These complications were prevented by modifying the surgical technique accordingly.\n\nConclusions. We developed and optimized a reproducible model of porcine kidney autotransplantation. Herein we have demonstrated the importance of a proper surgical anastomotic technique to avoid inflow or outflow obstruction that might jeopardize posttransplant kidney function. This clinically relevant model offers the possibility to study various aspects related to

kidney preservation without the interference of an

allogeneic immune response.”
“Litchi chinensis pericarp from litchi processing waste is an important plant source of A-type procyanidins, which were considered a natural dietary supplement because of their high biological activity in vivo. Litchi pericarp oligomeric procyanidins (LPOPCs) did not selectively modify the growth of Streptococcus thermophilus and Lactobacillus casei-01 at concentrations of 0.25 and 0.5 mg/mL, and it was demonstrated that the two strains could transform procyanidins during their log period of growth by two different pathways. S. thermophilus was able to metabolize procyanidin A2 to its isomer, and L. casei could decompose flavan-3-ols into 3,4-hydroxyphenylacetic acid, 4-hydroxyphenylpropionic LBH589 cost acid, m-coumaric acid, and p-coumaric acid. The total

antioxidant capability (T-AOC) of LPOPCs before and after microbial incubation was estimated, and the results suggested that probiotic bacteria bioconversion is a feasible and efficient method to convert litchi pericarp procyanidins to a more effective antioxidant agent.”
“One-pot etherification reaction of aromatic Selleck MRT67307 and some aliphatic carbonyl compounds with organic halides in the presence of sodium hydride as a reducing reagent proceeded smoothly in dioxane, a polar solvent with higher boiling point, to provide desired ethers in moderate to high yields.”
“Finding the source of a fungal infection and selecting the most appropriate treatment for candidemia is often challenging for physicians, especially when the patient has a complex medical history We describe the case of a 48-year-old woman who had persistent candidemia after undergoing explantation of a left ventricular assist device. The source of the infection was found to be a right atrial thrombus. The mass was removed, and the patient underwent aggressive treatment with micafungin. Removal of the right atrial mass, followed by potent antifungal treatment, resulted in a successful recovery (Tex Heart Inst J 2012;39(3):390-2)”
“In forensic science, identifying a tissue where a forensic specimen was originated is one of the principal challenges.

Karyotyping and surface immunophenotyping of the cells were perfo

Karyotyping and surface immunophenotyping of the cells were performed.\n\nResults:\n\nIt

was found that a population of ligament-derived cells could be expanded and subcultured extensively. These cells were able to differentiate into osteoblasts, chondrocytes and adipocytes under appropriate inductions. Their phenotypic characteristics were similar to those of bone marrow mesenchymal stem cells. Karyotyping was normal after serial passage.\n\nConclusions:\n\nIn OICR-9429 nmr summary, our study demonstrates that human multipotent stem cells can be isolated and expanded from human ACL and PCL, which are easily obtained from patients following total knee or cruciate ligament reconstructive surgery. Self-renewal and mesodermal differentiation potential of these cells make them a viable alternative source for use in regenerative medicine.”
“The first lineage decision during mouse development is the establishment of trophectoderm and inner cell mass lineages, morphologically distinguishable at the blastocyst stage. The Caudal-like transcription factor Cdx2 is required for repression of inner cell mass genes Oct4 and Nanog in the trophectoderm. Expression of Cdx2 in the

trophectoderm is thus one of the earliest known events in lineage determination. However, it is not clear whether Rabusertib molecular weight the Cdx2 expression pattern is the cause or the consequence of this first lineage decision. Here, we show that Cdx2 is initially ubiquitously expressed, and becomes progressively upregulated in outside, future trophectoderm cells prior to blastocyst formation. Ubiquitous Cdx2 expression begins around the time of cell polarization, selleckchem but we show that cell polarization is independent of zygotic Cdx2. Finally, we show functionally that Cdx2 is downstream of lineage allocation since Cdx2 mutant cells, which show cell-autonomous defects in

expression of Oct4, Nanog, and the tropbectoderm marker Eomesodermin, do not preferentially contribute to inner cell mass in chimeric blastocysts. Cdx2 therefore appears to act downstream of the first lineage decision, suggesting that processes influencing lineage allocation or morphogenesis may regulate Cdx2 expression along the inside/outside axis of the embryo. (C) 2007 Elsevier Inc. All rights reserved.”
“Chemoresistance is a major issue for most gemcitabine-related chemotherapies. The overexpression of ribonucleotide reductase subunit M1 (RRM1) plays a key role in gemcitabine resistance. In this study, we synthesized a new highly acid-sensitive amphiphilic micelle material by conjugating hydrophilic poly-ethylene glycol with a hydrophobic stearic acid derivative (C18) using a hydrazone bond, which was named as PHC-2. A lipophilic prodrug of gemcitabine, 4-(N)-stearoyl gemcitabine (GemC18), was loaded into micelles prepared with PHC-2, a previously synthesized less acid-sensitive PHC-1, and their acid-insensitive counterpart, PAC.

32, 95% CI: 1 15-1 52) The study also showed that the RR of asth

32, 95% CI: 1.15-1.52). The study also showed that the RR of asthma events on a given day, as well as the average daily peak ozone concentration during the preceding 48-72 h, increased at cumulative ozone concentrations of 70 to 100 ppb and 100 ppb or more compared with ozone concentrations of less than 70 ppb (P < 0.05). We concluded that along with “good” weather conditions, efforts to reduce traffic congestion in Beijing during the Olympic Games were associated with a prolonged reduction in air pollution and significantly lower rates of adult asthma events. These data provide support for efforts

to reduce air pollution this website and improve health via reductions in motor vehicle traffic.”
“A simple topological graph T = (V(T). E(T)) is a drawing of a graph in the plane, where every two edges have at most one common point (an end-point or a crossing) and no three edges pass through a single crossing. Topological graphs G and H are isomorphic if H can be obtained from G by a homeomorphism of the sphere, and weakly isomorphic if G and H have the same set of pairs of crossing edges. We prove that the number of isomorphism classes of simple complete topological graphs on it vertices is 2((-)(n4)). We also show that the number of weak isomorphism classes of simple complete topological

JNK-IN-8 graphs with n vertices and ((n)(4)) crossings is at least 2(n(log n-O(1))), which improves the estimate of Harborth and Mengersen. (C) 2009 Elsevier Ltd. All rights reserved.”
“Background and Objectives: Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with various chronic abdominal pain syndromes including chronic pancreatitis. Here described is a large clinical

experience in SCS for severe chronic pancreatitis.\n\nMethods: SCS was trialed in 30 patients with chronic pancreatitis. PX-478 order SCS trials lasted 7-14 days (median 9 days). SCS lead tips were mostly positioned at the T5 (N = 10) or T6 (N = 10) vertebral level.\n\nResults: Twenty-four patients (80%) reported at least 50% pain relief on completion of the trial. Among these, pre-trial visual analog scale (VAS) pain scores averaged 8 +/- 1.6 (standard deviation) and opioid use averaged 165 +/- 120 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.67 +/- 2 cm (p < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 105 +/- 101 mg morphine equivalent a day. Six patients failed the trial; one was lost to follow-up; in three patients after the implantation, the system had to be removed due to infection or lead migration; and 20 were followed for the whole year. For 20 patients followed for the whole year, VAS pain scores remained low (3.6 +/- 2 cm; p < 0.001) at one year, as did opioid use (48.6 +/- 58 mg morphine equivalents).\n\nConclusions: SCS may be a useful therapeutic option for patients with severe visceral pain from chronic pancreatitis. Prospective trial is warranted.

The NU

The p38 MAPK pathway transducer made angles of 90 degrees, 60 degrees and 45 degrees with the surface of the phantom. The times to perform the procedures were significantly shorter and the needle visualisation was significantly better when using the needle guidance device. The residents ranked their satisfaction with the needle-guidance device

significantly better than the ‘free-hand’ technique. This device may be beneficial when performing ultrasound guided peripheral nerve blocks, especially by inexperienced operators.”
“Context. Malignant fungating wounds (MFW) result from cutaneous infiltration by carcinogenic cells. Fetid odor, profuse exudate, pain, and infection are common symptoms that add to the physical and psychological suffering

of patients with MFW. The topical treatment of MFW remains controversial.\n\nObjectives. 17DMAG mouse To collect evidence about topical treatments to control the odor of MFW.\n\nMethods. Fourteen sources of data were used, without restriction in terms of language, period, or study design. The patient, intervention, comparison, and outcome strategy for the development of research questions yielded 334 descriptors related to oncology, MFW, topical treatments, medications, and symptoms of these lesions. Data from the abstracts of these articles were extracted by two independent researchers and decisions were reached by consensus among them. Through an analysis of these abstracts, studies that broached the topic of MFW odor were selected. These studies were analyzed in their entirety and were classified according to quality, levels of evidence, and grade of recommendation.\n\nResults. Of 11,111

studies identified, 325 (2.93%) made reference to the control of some symptoms of MFW by means of topical interventions: 12.4% related to odor, 16.8% to exudate, 17.8% to bleeding, 31.0% to pain, and 22.0% to MFW-related infection. Within the 59 studies that analyzed odor control, seven were clinical trials (35%), five were case series (25%), and eight (40%) were case studies. Eleven topical treatments EPZ5676 nmr were identified. Topical metronidazole and Mesalt(R) dressing yielded 213 level of evidence or B grade of recommendation. Activated carbon dressing and curcumin ointment yielded 2c level of evidence or B grade of recommendation. C and D grades of recommendation were observed for seven topical treatments: topical arsenic trioxide, essential oils, green tea extract, hydropolymer dressings, antiseptic solutions, hydrogels, and debridement enzymes. The variety of interventions and of the methodological quality of the studies did not allow for meta-analysis.\n\nConclusion. Of the 59 studies of odor, 20 fulfilled all the criteria for inclusion.

Results were validated in an independent intramural cohort (n

\n\nResults were validated in an independent intramural cohort (n = 34). Results: Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates

examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy (P < 0.01). The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a nine-fold greater risk of death at two years.\n\nConclusions: Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA 5-Fluoracil purchase repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment. Clin Cancer Res; 17(7); 2035-43. (C)2011 AACR.”
“Survivorship care plans www.selleckchem.com/products/ca3.html (SCPs) are intended to educate survivors and providers about survivors’ transition

from cancer treatment to follow-up care. Using a survey of 23 cancer programs in the South Atlantic United States, we (1) describe the prevalence and barriers to SCP use and (2) assess relationships between SCP use and (a) barriers and (b) cancer program characteristics. Most cancer programs (86 %) reported some SCP use; however, less than a quarter of cancer programs’ providers Tozasertib had ever used an SCP. The majority (61 %) began using SCPs because of professional societies’ recommendations. Key barriers to SCP use were insufficient organizational resources (75 %) and systems for SCP use. We found patterns in SCP use across location, program type, and professional society membership. Most cancer programs have

adopted SCPs, but use remains inconsistent. Efforts to promote SCP use should address barriers, particularly in cancer programs that are susceptible to barriers to SCP use.”
“Objectives: To analyze the nasal superficial arterial vasculature and to compare these anatomic findings with the results of ultrasonography Doppler investigations to evaluate nasal blood flow in physiological and pathologic conditions.\n\nMethods: We performed 40 ultrasonography Doppler investigations in patient volunteers, 20 facial anatomic dissections in fresh cadavers, and a review of the literature on nasal blood supply. In cadavers, facial arteries were dissected to analyze nasal arterial supply.\n\nResults: When the facial artery, the ophthalmic artery, or both were compressed on 1 side in volunteers, blood flow inversion was proved by ultrasonography Doppler investigation at the level of the nasal area. These results confirm anatomic findings that demonstrate a polygonal system.

The findings have important implications in further preclinical d

The findings have important implications in further preclinical development of TMS for treatment of human diseases. (C) 2014 AIP Publishing LLC.”
“Long-term pituitary down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist for 3-6 months prior to IVF/intracytoplasmic sperm injection (ICSI) improves clinical pregnancy rates in endometriosis patients. However, some discussion about this treatment strategy still exists. This retrospective study from a tertiary-care university hospital examined the efficacy and safety of IVF/ICSI with and without

long-term pituitary down-regulation in MLN2238 in vivo severe endometriosis patients (surgically confirmed American Society for Reproductive Medicine stages III and IV). All first IVF/ICSI treatment cycles between January 2009 and January 2012 were analysed. In patients treated with (n = 68) and without (n = 45) long-term pituitary down-regulation, 13 (19.1%) versus nine (20.0%) ongoing pregnancies after fresh embryo transfer (adjusted OR 0.58,

95% CI 0.18-1.86,) and 24 (35.3%) versus 10 (22.2%) ongoing pregnancies after fresh and cryopreserved embryo transfers (adjusted OR 1.62, 95% CI 0.60-4.38) were accomplished, respectively. Three complications (2.7%) and three recurrences (2.7%) were reported, only in patients treated with long-term pituitary down-regulation. The 1-year cumulative endometriosis recurrence rate was 7.3%. IVF/ICSI ATM/ATR inhibitor drugs in patients with severe endometriosis is safe with low complication and recurrence rates.

A favourable effect, albeit non-significant, of long-term pituitary down-regulation in achieving an ongoing pregnancy Ferroptosis assay was observed only after including cryopreserved embryo transfers. (C) 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“Carotene desaturation, an essential step in the carotenoid biosynthesis pathway, is catalyzed by two carotene desaturases, phytoene desaturase (PDS) and f-carotene desaturase (f-carotene desaturase, ZDS). Full-length cDNAs designated TaPDS and TaZDS were cloned from wheat (Triticum aestivum cv. Chinese Spring) respectively, using the rapid amplification of cDNA ends (RACE) approach. The cDNA of TaPDS sequence was 2076 bp long, containing a 1731 bp open reading frame (ORF) which deduced protein having 576 amino acid residues with predicted molecular mass of 64.3 kDa and having a putative transit sequence for plastid targeting in the N-terminal region. While the cDNA sequence of TaZDS was 2150 bp long, contained an ORF sequence of 1707 bp, and encoded a putative protein of 568 amino acid residues with an estimated molecular mass of 62.5 kDa. Phylogenetic analysis demonstrated that TaPDS and TaZDS showed high homology with other PDSs and ZDSs in higher plant species, respectively. Moreover, sequences analysis also showed a high degree of conservation among plant PDSs and ZDSs.

In addition, taurine prevented the ex vivo damage caused by tert-

In addition, taurine prevented the ex vivo damage caused by tert-butyl hydroperoxide in rat liver slices. These experimental data show that taurine,

at different physiological concentrations efficiently scavenges many reactive oxygen and nitrogen species. This finding supports the hypothesis that the antioxidant properties of taurine may be critical for the maintenance of cellular functions, and it suggests a more important function of taurine that requires further investigation.”
“In this study, the effects of the ammonium sulphate intoxication on the blood antioxidant /oxidant status were investigated in Sakiz crossbred lambs. For that, circulating blood urea nitrogen (BUN), nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), beta-carotene, retinol and ceruloplasmin concentrations were measured in 6 lambs accidentally poisoned with ammonium sulphate and in 6 healthy control lambs. Oral treatment with 10% glutamic acid (1g/kg), 3-deazaneplanocin A manufacturer 2.5% acetic acid (2.5 mL/kg) and vitamin A (400 IU/kg) was daily administered to diseased animals for five days. Poisoned lambs exhibited neurological signs (sleepiness, ataxia, tonic and clonic spasms) coupled to a rumen atony and acceleration of

heart and respiratory rates compared to healthy controls. Biochemically, the circulating MDA, NO and BUN concentrations were markedly increased and the GSH, beta-carotene and vitamin A concentrations were significantly depressed compared to healthy controls whereas the ceruloplasmin concentrations were not significantly

altered. After treatment, Tyrosine Kinase Inhibitor Library solubility dmso clinical and biochemical signs were significantly alleviated but, however 2 lambs Bcl-2 inhibitor died. For them, the histopathological examinations after haematoxylin-eosin staining revealed cell degeneration in liver, lungs and kidney associated to mononuclear cell infiltrates and proliferation of Kiipffer cells. These results clearly showed the occurrence of an oxidative stress induced by ammonium sulphate poisoning leading to cell damage and proved the efficiency of a treatment based on organic acids and retinol supplementation.”
“Let f(n) be the maximum integer such that for every set F of at most f(n) vertices of the hypercube Q (n) , there exists a cycle of length at least 2 (n) -2|F| in Q (n) -F. Castaeda and Gotchev conjectured that . We prove this conjecture. We also prove that for every set F of at most (n (2)+n-4)/4 vertices of Q (n) , there exists a path of length at least 2 (n) -2|F|-2 in Q (n) -F between any two vertices such that each of them has at most 3 neighbors in F. We introduce a new technique of potentials which could be of independent interest.”
“Measles virus (MV) is one of the most transmissible microorganisms known, continuing to result in extensive morbidity and mortality worldwide. While rare, MV can infect the human central nervous system, triggering fatal CNS diseases weeks to years after exposure.

aeruginosa The main resistant microorganism in diabetic foot inf

aeruginosa. The main resistant microorganism in diabetic foot infections requiring hospitalization was methicillin-resistant golden staphylococcus, which was found in 12% of the series. (C) 2007 Elsevier Espana, S.L All rights reserved.”
“Background. Self-efficacy appears to be an important predictor of functional recovery for women with urinary incontinence, but no specific Spanish-language questionnaires for measuring pelvic-floor exercise self-efficacy exist.\n\nObjective. The aim of this study was to design a valid and reliable Spanish version of the Broome Pelvic Muscle Self-Efficacy Scale to measure self-efficacy, as perceived by women with

check details urinary incontinence, in performing pelvic-floor exercises.\n\nDesign. This was an observational validation study.\n\nMethods. Translation-back translation selleck chemicals llc was used to design the survey, and then the survey was validated with a sample of 119 women who were incontinent and had undergone a pelvic-floor exercise training program. The reliability and construct validity of the questionnaire were assessed. Descriptive statistics were used to score the questionnaire. Internal consistency was evaluated with the Cronbach alpha coefficient and the Pearson correlation

coefficient. Exploratory factor analysis with both the principal components extraction method and the varimax rotation method was used to assess construct validity.\n\nResults. The reliability coefficient (Cronbach alpha=.91) and the correlations among items were high: The factor analysis

revealed that 6 main factors accounted for 75.8% of the variance.\n\nLimitations. Conclusions regarding the validity of the questionnaire should be drawn with caution because of the inability to assess criterion-related validity.\n\nConclusions. Sotrastaurin cost The Spanish version of the Broome questionnaire for self-efficacy appears to be useful as a measuring tool for a psychometrically accurate, clinically relevant estimation of women’s self-efficacy in performing pelvic-floor exercises.”
“Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown the potential of this plant as an agent for the control of cariogenic biofilms. In this study, the main antibacterial components of the plant were identified by correlating gas chromatography-mass spectrometry data with the antibacterial activity of chloroform and n-hexane fractions and then evaluating the activity of the most potent antibacterial component against Streptococcus mutans UA159 biofilms. The most potent antibacterial component was linoleic acid, a main component of the n-hexane fraction. Linoleic acid reduced viability in a dose dependent manner and reduced biofilm accumulation during initial and mature biofilm formation. Furthermore, when the biofilms were briefly treated with linoleic acid (10 min/treatment, a total of six times), the dry weight of the biofilms was significantly diminished.

(C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society

(C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands AZD0530 with neonatal diabetes. Functional studies showed

that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription,

including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with selleck chemicals an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs.-2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence

elements that regulate the biosynthesis of insulin in man.”
“A combination of analytical techniques capable of elemental and microstructural characterisation was used for the identification of ancient gilding technology and bronze metallurgy. EDXRF, micro-EDXRF, SEM-EDS analysis and metallographic examinations were applied in the study of artefacts dating to the end of the second millennium BC from Crasto de So Romo in Central Portugal. Results report to the finding of an exceptional gilded copper nail among bronze GSK1838705A Protein Tyrosine Kinase inhibitor artefacts with 9 wt.% to15 wt.% tin and minute other metallic impurities. Additionally, analysis of a crucible fragment points out for bronze production at the archaeological site. EDXRF and micro-EDXRF analysis made on the copper nail showed that it was gilded only on the front side of the head, and that the gold layer has been lost in the most exposed areas. SEM-EDS analysis showed that the gold layer has 5-8 A mu m in thickness and is covered with a thick corrosion layer. The gilding technique is discussed based on the gold layer composition and gold/copper substrate interface. So far, this object seems to be the first diffusion gilded artefact identified in the Portuguese territory dated to Late Bronze Age.

All rights reserved “
“p,p’-DDE, the major metabolite of dic

All rights reserved.”
“p,p’-DDE, the major metabolite of dichlorodiphenoxytrichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. However, the mechanism underlying its male reproductive toxicity remains limited. Our previous studies have demonstrated that p,p’-DDE could induce mitochondria-mediated apoptosis of cultured rat Sertoli cells. In the present study, we investigated mitogen-activated protein kinase pathways as well as other mitochondria-related molecules including

Panobinostat order Bax family members and cytochrome c. Results showed that p,p’-DDE could induce oxidative stress-mediated p38 and JNK phosphorylation. In addition, elevated mRNA levels of cytochrome c and ratios of bax/bcl-w and bak/bcl-w were induced by p,p’-DDE treatment, which could be inhibited by click here RNA synthesis inhibitor (actinomycin D). p,p’-DDE-induced apoptosis was blocked by NAC (N-acetyl-L-cystein) preincubation and attenuated by pretreatment with p38 inhibitor (SB202190) or actinomycin D, but not with JNK inhibitor (SP600125). All of the findings suggested that oxidative stress-mediated p38 MAPK pathway and the balance between pro- and anti-apoptotic box-gene family might play

critical roles in p,p’-DDE-induced apoptosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Nowadays, drug development requires large-scale studies to show the real clinical benefit for the patients, which means recruiting a sufficient number of patients, even internationally. As global studies enable simultaneous delivery of new drugs and sharing www.selleckchem.com/products/AC-220.html of safety information around the world, multinational studies now account for around 20% of Japanese clinical studies. Until recently, drug development has been centered in Western countries, but interest in Asian regions has increased. In this environment, one important factor in drug development is ethnicity. Various cancers show regional patterns in their incidence, and some (such as liver cancer and gastric cancer) show high incidences in Asian countries. Ethnic factors including genetic differences, such as the CYP drug-metabolizing enzymes in the liver and gene mutations, may result in different

drug responses in terms of efficacy and safety. Examples of ethnic differences in drug responses were seen with gefitinib, which showed a different efficacy data, and with sunitinib, showing a clearly different toxicity profile between the West and Asia. Therefore, ethnic differences need to be taken into account in the early phase of drug development, and Asian countries need to be involved early in clinical development. Asian collaboration among physicians and networks of specialists is also important, and there is good potential for successful establishment of the infrastructure needed for collaborative clinical trials. Establishment of a so-called third development center in Asian countries that will complement the USA and European centers is highly desired.”
“Background.