Background: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict ...clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy. Patients and methods: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-h infusion at day 1 plus leucovorin 20 mg/m2 over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1–2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry. Results: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037). Conclusion: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.
Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and ...metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis. We found that the loss of STAT3 in ECs did not affect primary Lewis lung carcinoma (LLC) tumor growth, but it reduced in vivo LLC metastasis in experimental and spontaneous metastasis models. Mechanistically, STAT3 activation upregulated cell adhesion molecule expression, including E-selectin and P-selectin, in murine endothelial MS-1 cells treated with tumor cell-conditioned media in vitro and in pre-metastatic lungs of tumor-bearing mice in vivo. We also found that both E-selectin and P-selectin were, at least in part, responsible for STAT3-induced adhesion and invasion of LLC cells through an EC monolayer. However, tumor cell-conditioned media from B16F10 melanoma cells did not activate STAT3 in MS-1 cells. As a result, EC STAT3 knockout did not affect B16F10 melanoma cell metastasis. In addition, various human cancer cells activated STAT3 in human ECs (HUVECs), resulting in increased cell adhesion molecule expression. Collectively, our findings demonstrate that STAT3 activation in ECs promotes tumor metastasis through the induction of cell adhesion molecules, demonstrating a role for ECs in response to tumor cells during tumor metastasis.
Background: ABCB1 is responsible for multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs. There is a controversy whether ABCB1 gene ...polymorphisms correlate with survival and response in cancer patients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancer patients with ABCB1 gene polymorphisms 2677G>T/A or 3435C>T. Patients and methods: Patients with metastatic breast cancer were treated with 175 mg/m2 paclitaxel per 3-week cycle. Peripheral blood mononuclear cells from patients were used to genotype ABCB1 2677G>T/A and 3435C>T polymorphisms. Genotypes were investigated for their association with tumor response, survival, toxicity, and chemoresistance. Results: ABCB1 3435 CT showed a significantly lower disease control rate than the CC genotype (P = 0.025). ABCB1 3435 CT was correlated with shorter overall survival (OS) in Cox regression analysis (P = 0.026). The 2677 GG genotype showed a significant association with chemoresistance to paclitaxel and anthracycline (P = 0.04 and 0.04, respectively). None of the ABCB1 genotypes correlated with toxicity. Conclusions: ABCB1 genotypes may be a predictor of paclitaxel activity as well as a prognostic factor in metastatic breast cancer patients.
Currently, the characteristics of carotid plaques are considered important factors for identifying subjects at high risk of stroke. This study aimed to test the hypothesis that carotid plaque ...composition assessed by CTA is associated with an increased risk of future major adverse cardiovascular events among asymptomatic subjects with moderate-to-severe carotid artery stenosis.
This single-center, retrospective cohort study included 194 carotid plaques from 176 asymptomatic subjects with moderate-to-severe carotid artery stenosis. The association of CTA-determined plaque composition with the risk of subsequent adverse cardiovascular events was analyzed.
During a median follow-up of 41 months, the adverse cardiovascular event incidence among 194 carotid plaques was 19.6%. There were significant differences in plaque Hounsfield units (
< .001) and spotty calcium presence (
< .001) between carotid plaques from subjects with and without subsequent adverse cardiovascular events. Multivariable analysis revealed carotid plaque Hounsfield unit density (
< .001) and spotty calcium (
< .001) as independent predictors of subsequent adverse cardiovascular events. In association with moderate carotid artery stenosis, the plaque Hounsfield unit values were significantly lower among carotid plaques from subjects who experienced subsequent adverse cardiovascular events (
= .002), strokes (
= .01), and cardiovascular deaths (
= .04); the presence of spotty calcium was significantly associated with the occurrence of adverse cardiovascular events (
= .001), acute coronary syndrome (
= .01), and cardiovascular death (
= .04).
Carotid plaque Hounsfield unit density and spotty calcium were independent predictors of a greater risk of adverse cardiovascular event occurrence.
Novel blue‐light‐emitting materials, 9,10‐bis(1,2‐diphenyl styryl)anthracene (BDSA) and 9,10‐bis(4′‐triphenylsilylphenyl)anthracene (BTSA), which are composed of an anthracene molecule as the main ...unit and a rigid and bulky 1,2‐diphenylstyryl or triphenylsilylphenyl side unit, have been designed and synthesized. Theoretical calculations on the three‐dimensional structures of BDSA and BTSA show that they have a non‐coplanar structure and inhibited intermolecular interactions, resulting in a high luminescence efficiency and good color purity. By incorporating these new, non‐doped, blue‐light‐emitting materials into a multilayer device structure, it is possible to achieve luminance efficiencies of 1.43 lm W–1 (3.0 cd A–1 at 6.6 V) for BDSA and 0.61 lm W–1 (1.3 cd A–1 at 6.7 V) for BTSA at 10 mA cm–2. The electroluminescence spectrum of the indium tin oxide (ITO)/copper phthalocyanine (CuPc)/1,4‐bis(1‐naphthylphenyl)‐aminobiphenyl (α‐NPD)/BDSA/tris(9‐hydroxyquinolinato)aluminum (Alq3)/LiF/Al device shows a narrow emission band with a full width at half maximum (FWHM) of 55 nm and a λmax = 453 nm. The FWHM of the ITO/CuPc/α‐NPD/BTSA/Alq3/LiF/Al device is 53 nm, with a λmax = 436 nm. Regarding color, the devices showed highly pure blue emission ((x,y) = (0.15,0.09) for BTSA, (x,y) = (0.14,0.10) for BDSA) at 10 mA cm–2 in Commission Internationale de l'Eclairage (CIE) chromaticity coordinates.
Deep‐blue organic light‐emitting diodes have been realized using new blue‐light‐emitting materials that contain an anthracene molecule as the main backbone and 1,2‐diphenylstyryl and tetraphenylsilane as the side units. The electroluminescence spectra of the non‐doped devices show a narrow emission band, almost perfectly matching the “standard” blue (see Figure). Thin films of the material are of high quality and thermally stable.
Yogurt is a healthy dairy food fermented by lactic acid bacteria (LAB). Because consumers demand healthier and more nutritious yogurt, numerous substances have been used to supplement yogurt. Chia ...seed has been reported to contain abundant phenolic compounds, dietary fiber, and n-3 fatty acids and therefore is a potential functional food additive. The aim of this study was to investigate the influence of chia seed extracts on the physicochemical and bioactive properties of set-type yogurt. Yogurt was fortified with chia seed water extract (CSWE) or chia seed ethanol extract (CSEE) at 0.05 or 0.1% (vol/vol). Results showed that supplementation with CSWE or CSEE significantly accelerated the fermentation rate and growth of LAB. Both CSWE and CSEE improved the viscosity, syneresis, and water-holding capacity of yogurt. The radical scavenging activity of yogurt was increased with both extracts, and the 0.1% CSEE yogurt exhibited the highest radical scavenging activity. Furthermore, 0.1% CSEE yogurt significantly inhibited lipopolysaccharide-induced production of hydrogen peroxide in human colon cells. Addition of chia seed extract improves the growth of LAB, the physiochemical properties, and the health-beneficial effects of set-type yogurt.
Background
Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal ...infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models.
Methods
Asthma phenotypes were analyzed in response to various allergen‐induced experimental asthma using Nox2‐deficient mice and recombinase gene‐activating‐1‐deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T‐cell activation, levels of activation‐induced cell death (AICD), and regulatory T (Treg)‐cell differentiation in Nox2‐deficient T cells.
Results
Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2‐null mice regardless of dose and route of various allergens. Nox2‐deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg‐cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production.
Conclusion
Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T‐cell‐intrinsic manner.
Diabet. Med. 27, 1033–1040 (2010)
Aims This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy.
Methods An open, ...randomized, comparative study was conducted. Subjects with painful symmetric neuropathy in the lower limbs and mean pain‐intensity score ≥ 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36‐item Short Form Health Survey, average pain intensity and sleep disturbance.
Results One hundred and sixty‐three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 ± 1.6; gabapentin 6.3 ± 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A −3.1 ± 2.0; gabapentin −2.7 ± 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores.
Conclusion This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.
We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish ...this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.
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