Large scale gene expression pro®ling was carried out on laser capture microdissected (LCM) tumor and normal oral epithelial cells and analysed on high-density oligonucleotide microarrays. About 600 genes were found to be oral cancer associated. These oral cancer associated genes include oncogenes, tumor suppressors, transcription factors, xenobiotic enzymes, metastatic proteins, di erentiation markers, and genes that have not been implicated in oral cancer. The database created provides a veri®able global pro®le of gene expression during oral carcinogenesis, revealing the potential role of known genes as well as genes that have not been previously implicated in oral cancer. Oncogene (2001) 20, 6196 ± 6204.
Abstract. Black carbon (BC) is the dominant absorbing aerosol in the atmosphere, and plays an important role in climate and human health. The optical properties and cloud condensation nuclei (CCN) activity of soot depend on the amounts (both relative and absolute) of BC and non-refractory material in the particles. Mixing between these two components is often represented in models by a core / shell coated sphere. The single-particle soot photometer (SP2) is one of, if not the only, instrument capable of reporting distributions of both core size and coating thickness. Most studies combine the SP2's incandescence and 1064 nm scattering data to report coating properties, but to date there is no consistency in the assumed values of density and refractive index of the core that are used in these calculations, which can greatly affect the reported parameters such as coating thickness. Given that such data are providing an important constraint for model comparisons and comparison between large data sets, it is important that this lack of consistency is addressed. In this study we explore the sensitivity of the reported coatings to these parameters. An assessment of the coating properties of freshly emitted, thermodenuded ambient particles demonstrated that a core density of 1.8 g cm−3 and refractive index of (2.26–1.26i) were the most appropriate to use with ambient soot in the Los Angeles area. Using these parameters generated a distribution with median shell / core ratio of 1.02 ± 0.11, corresponding to a median absolute coating thickness of 2 ± 8 nm. The main source of statistical error in the single-particle data was random variation in the incandescence signals. Other than the sensitivity to core refractive index, the incandescence calibration was the main source of uncertainty when optically determining the average coatings. The refractive index of coatings was found to have only a minor influence. This work demonstrates that using this technique the SP2 can accurately determine the average mixing state (externally or internally mixed) of ambient soot within the precision of the instrument calibration. Ambient coatings were measured up to a median shell / core ratio of 1.50 ± 0.11, meaning that this technique is able to resolve absolute changes in mixing state. However, when different core parameters were used, the core / shell ratio and the coating thickness were shown to be offset by amounts that could be larger than the atmospheric variability in these parameters, though the results have a similar precision. For comparison, using the core parameters that resulted in the thickest coatings, on the same thermodenuded fresh particles as before, generated a median shell / core ratio of 1.39 ± 0.11, corresponding to a median absolute coating thickness of 30 ± 8 nm. These results must be taken into account when comparing BC coatings measured using this technique, or if using these data for optical or CCN calculations. We have determined the most appropriate values of BC density and refractive index to use to measure mixing state at 1064 nm where particle morphology has only a minor effect, but appropriate values to use for optical calculations of nonspherical particles at visible wavelengths will also be subject to similar, significant uncertainties. Without similar constraints as those provided here, constraining the behaviour of BC particles in models using field data will be subject to large systematic measurement uncertainties.
Aberrant expression of miR-335 has been frequently reported in cancer studies, suggesting that there is a close correlation between miR-335 and cancer during its development, progression, metastasis and prognosis. The expression of miR-335 in gastric cancer and its effects are not known. Relative expression of miR-335 in 4 gastric cancer cell lines and in 70 gastric cancer tissues was confirmed by real-time quantitative reverse transcriptase-PCR compared with controls. Transwell cell migration and Matrigel invasion assay in vitro and metastasis formation assay in vivo were used to examine the effects of miR-335 expression on gastric cancer cell invasion and metastasis. The effect of miR-335 expression on gastric cancer cell proliferation was estimated by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Luciferase reporter assay and western blot were used to examine the potential target genes and related pathways. Gene silencing with small-interfering RNA was used to examine the effects of target genes on gastric cancer cell invasion. miR-335 was dramatically downregulated in gastric cancer cell lines than in the normal gastric cell line GES-1. Low expression of miR-335 was significantly associated with lymph-node metastasis, poor pT stage, poor pN stage and invasion of lymphatic vessels. Overexpression of miR-335 suppressed gastric cancer cell invasion and metastasis in vitro and in vivo, but has no significant effects on cell proliferation. Furthermore, miR-335 might suppress gastric cancer invasion and metastasis by targeting Bcl-w and specificity protein 1 (SP1). Taken together, our results provide evidence that miR-335 might function as a metastasis suppressor in gastric cancer by targeting SP1 directly and indirectly through the Bcl-w-induced phosphoinositide 3-kinase-Akt-Sp1 pathway. miR-335 showing altered expression at different stages of gastric cancer could be a target for gastric cancer therapies and could be further developed as a potential prognostic factor.
Background: The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (21377GRA) and FASL (2844TRC) and risk of oesophageal cancer. Objective: To examine the contribution of these polymorphisms to risk of developing lung cancer. Methods: Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. Results: Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS 21377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL 2844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS 21377AA and FASL 2844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. Conclusion: These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.
Background/Objectives: To evaluate the association between body mass index (BMI) and incident hypertension in a cohort of rural women in the Chinese population. Subjects/Methods: A population-based sample of 11 468 rural Chinese women aged X35 years and free from hypertension at baseline were followed-up from 2004-2006 to 2008. We calculated BMI from measured weight and height. Incident hypertension was defined as systolic blood pressure (BP) X140 mm Hg, diastolic BPX90 mm Hg or current use of antihypertensive medications. Results: During a median follow-up of 28 months, 2666 participants developed hypertension. Higher baseline BMI, even within the 'normal' range, was consistently associated with an increased risk of hypertension. Compared with participants in the lowest BMI quintile (18.5-21.1 kg/m 2 ), the multivariable-adjusted relative risks (95% confidence interval) of developing hypertension for women with a BMI of 21.2 to 22.4, 22.5 to 23.7, 23.8 to 25.4 and X25.4 kg/m 2 were 1.200 (1.058-1.361), 1.250 (1.100-1.419), 1.466 (1.291-1.666) and 1.785 (1.584-2.012), respectively (P for trend, o0.001). Further adjustment for baseline BP did not substantially alter these results. We found similar associations using other BMI categories and after excluding women with smoking history at baseline. The pattern of association also existed among old women (age X55 years). Conclusions:In this large cohort, we found a strong gradient association between higher BMI and increased risk of hypertension, even among older women within the normal BMI range. Clinicians should emphasize the importance of weight management for the primary prevention of hypertension in rural women in the Chinese population.
The prevalence of and associated risk factors for isolated systolic hypertension, as defined by the Joint National Committee (JNC)-6 classification, were investigated in the rural population of Liaoning Province, China. A total of 45,925 people aged 35 years or older were examined in a cross-sectional study. Overall, the prevalence of isolated systolic hypertension was 10.6% (males 10.1%; females 11.2%). The prevalence of isolated systolic hypertension was positively correlated with age, gender, smoking status, alcohol intake, body mass index, salt intake and Mongolian race. This study showed that isolated systolic hypertension was very common in rural Chinese people and that many risk factors are linked with isolated systolic hypertension.
Objective:Passive scattering proton beam (PSPB) radiotherapy for accelerated partial-breast irradiation (APBI) provides superior dosimetry for APBI three-dimensional conformal photon radiotherapy (3DCRT). Here we examine the potential incremental benefit of intensity-modulated proton radiotherapy (IMPT) for APBI and compare its dosimetry with PSPB and 3DCRT.Methods:Two theoretical IMPT plans, TANGENT_PAIR and TANGENT_ENFACE, were created for 11 patients previously treated with 3DCRT APBI and were compared with PSPB and 3DCRT plans for the same CT data sets. The impact of range, motion and set-up uncertainties as well as scanned spot mismatching between fields of IMPT plans was evaluated.Results:IMPT plans for APBI were significantly better regarding breast skin sparing (p<0.005) and other normal tissue sparing than 3DCRT plans (p<0.01) with comparable target coverage (p=ns). IMPT plans were statistically better than PSPB plans regarding breast skin (p<0.002) and non-target breast (p<0.007) in higher dose regions but worse or comparable in lower dose regions. IMPT plans using TANGENT_ENFACE were superior to that using TANGENT_PAIR in terms of target coverage (p<0.003) and normal tissue sparing (p<0.05) in low-dose regions. IMPT uncertainties were demonstrated for multiple causes. Qualitative comparison of dose–volume histogram confidence intervals for IMPT suggests that numeric gains may be offset by IMPT uncertainties.Conclusion:Using current clinical dosimetry, PSPB provides excellent dosimetry compared with 3DCRT with fewer uncertainties compared with IMPT.Advances in knowledge:As currently delivered in the clinic, PSPB planning for APBI provides as good or better dosimetry than IMPT with less uncertainty.
Canopy temperature and incident photosynthetically active radiation were measured in experimental rice plots in Guangzhou, South China, during conditions which approximated those of the 'dry cold dew wind', a chilling phenomenon which is responsible for substantial yield reduction in rice. These field conditions were then reproduced in controlled environment photosynthetic measurement chambers. Mature plants of five varieties of rice were arranged to simulate a canopy in these chambers which was then exposed to a 3-day chilling treatment (21°C day/lO°C night) 14 days after anthesis. Canopy photosynthesis was measured before, during and after the chilling period. A Japonica-like cultivar, Hungarian-1 from Central Europe, and an Indica-like cultivar, Lemont from Texas, were markedly less sensitive to a chilling-dependent reduction in photosynthesis than were cultivars Gui Chao-2, Er Bai Ai and IR-8 from South-East China and The Philippines. The extent of chilling-dependent reduction in photosynthesis was greater if roots of plants in the simulated canopy were allowed to track air temperature at night. This led to a 5-7°C differential between root and air temperature in the morning and was associated with a midday depression of photosynthesis in all varieties. If root temperature was kept at 20°C during the day and night and air temperature controlled at 21°C day/ 10°C night, the effects of chilling on photosynthesis were much less pronounced.These changes in canopy photosynthesis following chilling treatments were correlated with changes in leaf level parameters. The level of soluble sugars and starch in leaves was found to remain high during the first cool night and to increase further during the next day. In cultivars which showed pronounced inhibition of canopy photosynthesis throughout the chilling treatment (Gui Chao-2, IR-8), soluble sugars remained at high levels until temperatures were returned to control values. In the less sensitive cultivar, Hungarian-1, soluble sugars declined throughout the chilling treatment. These results suggest inhibition of photosynthesis may be associated with sugar retention in leaves of rice at low temperatures, and imply differences between cultivars in this response. Other photosynthetic parameters monitored included the maximum rate of light and COz saturated photosynthesis, the quantum yield of photosynthesis, and FO and F,IF, of chlorophyll fluorescence at 77K. Surprisingly, Hungarian-1, the cultivar which showed least impairment of canopy photosynthesis showed greater reduction in quantum yield and larger changes in fluorescence parameters during the chilling treatments. These changes were readily reversible and may be related to the more horizontal leaf habit of this cultivar compared with the more vertical orientation of leaves in the other cultivars. These observations imply that assimilate regulation of photosynthetic metabolism, rather than light dependent damage to primary photosynthetic processes, underlies low temperature effects on yield of rice during grain fill...
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