Association of Urinary N7-(1-hydroxyl-3-buten-1-yl) Guanine (EB-GII) Adducts and Butadiene-Mercapturic Acids with Lung Cancer Development in Cigarette Smokers.

Approximately 10% of smokers will develop lung cancer. Sensitive predictive biomarkers are needed to identify susceptible individuals. 1,3-Butadiene (BD) is among the most abundant tobacco smoke carcinogens. BD is metabolically activated to 3,4-epoxy-1-butene (EB), which is detoxified via the glutathione conjugation/mercapturic acid pathway to form monohydroxybutenyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA). Alternatively, EB can react with guanine nucleobases of DNA to form N7-(1-hydroxyl-3-buten-1-yl) guanine (EB-GII) adducts. We employed isotope dilution LC/ESI-HRMS/MS methodologies to quantify MHBMA, DHBMA, and EB-GII in urine of smokers who developed lung cancer (N = 260) and matched smoking controls (N = 259) from the Southern Community Cohort (white and African American). The concentrations of all three biomarkers were significantly higher in smokers that subsequently developed lung cancer as compared to matched smoker controls after adjusting for age, sex, and race/ethnicity (p < 0.0001 for EB-GII, p < 0.0001 for MHBMA, and p = 0.0007 for DHBMA). The odds ratio (OR) for lung cancer development was 1.63 for MHBMA, 1.37 for DHBMA, and 1.97 for EB-GII, with a higher OR in African American subjects than in whites. The association of urinary EB-GII, MHBMA, and DHBMA with lung cancer status did not remain upon adjustment for total nicotine equivalents. These findings reveal that urinary MHBMA, DHBMA, and EB-GII are directly correlated with the BD dose delivered via smoking and are associated with lung cancer risk.

Effects of aluminum (Al) stress on the isoprenoid metabolism of two Citrus species differing in Al-tolerance.

Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.

Deoxyxylulose 5-Phosphate Synthase Does Not Play a Major Role in Regulating the Methylerythritol 4-Phosphate Pathway in Poplar.

The plastidic 2-C-methylerythritol 4-phosphate (MEP) pathway supplies the precursors of a large variety of essential plant isoprenoids, but its regulation is still not well understood. Using metabolic control analysis (MCA), we examined the first enzyme of this pathway, 1-deoxyxylulose 5-phosphate synthase (DXS), in multiple grey poplar (Populus × canescens) lines modified in their DXS activity. Single leaves were dynamically labeled with 13CO2 in an illuminated, climate-controlled gas exchange cuvette coupled to a proton transfer reaction mass spectrometer, and the carbon flux through the MEP pathway was calculated. Carbon was rapidly assimilated into MEP pathway intermediates and labeled both the isoprene released and the IDP+DMADP pool by up to 90%. DXS activity was increased by 25% in lines overexpressing the DXS gene and reduced by 50% in RNA interference lines, while the carbon flux in the MEP pathway was 25-35% greater in overexpressing lines and unchanged in RNA interference lines. Isoprene emission was also not altered in these different genetic backgrounds. By correlating absolute flux to DXS activity under different conditions of light and temperature, the flux control coefficient was found to be low. Among isoprenoid end products, isoprene itself was unchanged in DXS transgenic lines, but the levels of the chlorophylls and most carotenoids measured were 20-30% less in RNA interference lines than in overexpression lines. Our data thus demonstrate that DXS in the isoprene-emitting grey poplar plays only a minor part in controlling flux through the MEP pathway.

Histochemical studies on the distribution and accumulation of trans-polyisoprene in the rubber-producing plant Eucommia ulmoides.

Eucommia ulmoides rubber (EUR) is a high-quality natural rubber resource, which can be extracted from different organs of the Eucommia ulmoides tree. In this study, EUR was isolated from the leaves, barks, and pericarps, and the structural characteristics and physicochemical properties of EUR were systematically determined. The accumulation and distribution of EUR in different tissues were assessed through in situ observations combined with cellular and subcellular scales. The preliminary analyses indicated that the variations in the physicochemical properties of EUR across different tissues were associated with its accumulation microstructure. Further analyses by SEM and TEM showed that the initial cell differentiation and fusion resulted in the formation of tubular structures without any nucleus. A limited number of rubber particles were generated within the cytoplasm, concurrent with aggregation and fusion. Eventually, rubber particles filled the entire cytoplasm, and organelles disappeared to form highly aggregated filamentous structures. In addition, the number and area of EUR-containing cells were closely related to the organization sizes of barks and leaves. This study provided valuable insights into Eucommia ulmoides histology and the rubber industry.

Optimal seasonal schedule for the production of isoprene, a highly volatile biogenic VOC.

The leaves of many trees emit volatile organic compounds (abbreviated as BVOCs), which protect them from various damages, such as herbivory, pathogens, and heat stress. For example, isoprene is highly volatile and is known to enhance the resistance to heat stress. In this study, we analyze the optimal seasonal schedule for producing isoprene in leaves to mitigate damage. We assume that photosynthetic rate, heat stress, and the stress-suppressing effect of isoprene may vary throughout the season. We seek the seasonal schedule of isoprene production that maximizes the total net photosynthesis using Pontryagin's maximum principle. The isoprene production rate is determined by the changing balance between the cost and benefit of enhanced leaf protection over time. If heat stress peaks in midsummer, isoprene production can reach its highest levels during the summer. However, if a large portion of leaves is lost due to heat stress in a short period, the optimal schedule involves peaking isoprene production after the peak of heat stress. Both high photosynthetic rate and high isoprene volatility in midsummer make the peak of isoprene production in spring. These results can be clearly understood by distinguishing immediate impacts and the impacts of future expectations.

Computational investigation of cis-1,4-polyisoprene binding to the latex-clearing protein LcpK30.

Latex clearing proteins (Lcps) catalyze the oxidative cleavage of the C = C bonds in cis-1,4-polyisoprene (natural rubber), producing oligomeric compounds that can be repurposed to other materials. The active catalytic site of Lcps is buried inside the protein structure, thus raising the question of how the large hydrophobic rubber chains can access the catalytic center. To improve our understanding of hydrophobic polymeric substrate binding to Lcps and subsequent catalysis, we investigated the interaction of a substrate model containing ten carbon-carbon double bonds with the structurally characterized LcpK30, using multiple computational tools. Prediction of the putative tunnels and cavities in the LcpK30 structure, using CAVER-Pymol plugin 3.0.3, fpocket and Molecular Dynamic (MD) simulations provided valuable insights on how substrate enters from the surface to the buried active site. Two dominant tunnels were discovered that provided feasible routes for substrate binding, and the presence of two hydrophobic pockets was predicted near the heme cofactor. The larger of these pockets is likely to accommodate the substrate and to determine the size distribution of the oligomers. Protein-ligand docking was carried out using GOLD software to predict the conformations and interactions of the substrate within the protein active site. Deeper insight into the protein-substrate interactions, including close-contacts, binding energies and potential cleavage sites in the cis-1,4-polyisoprene, were obtained from MD simulations. Our findings provide further justification that the protein-substrate complexation in LcpK30 is mainly driven by the hydrophobic interactions accompanied by mutual conformational changes of both molecules. Two potential binding modes were identified, with the substrate in either extended or folded conformations. Whilst binding in the extended conformation was most favorable, the folded conformation suggested a preference for cleavage of a central double bond, leading to a preference for oligomers with 5 to 6 C = C bonds. The results provide insight into further enzyme engineering studies to improve catalytic activity and diversify the substrate and product scope of Lcps.

Incidencia, mortalidad y supervivencia al cáncer de próstata en Cali, Colombia, 1962-2011 / Prostate cancer in Cali, Colombia, 1962-2011: incidence, mortality and survival

Objetivo. Analizar la tendencia de las tasas de incidencia, mortalidad y supervivencia al cáncer de próstata (CP) en el periodo 1962-2011. Material y métodos. Con base en el Registro Poblacional de Cáncer en Cali (Colombia) y los registros de mortalidad de la Secretaría de Salud Pública Municipal se analizaron las tendencias de las tasas de incidencia, mortalidad y supervivencia por CP en Cali durante el periodo 1962-2011. Resultados. La incidencia de cáncer de próstata aumentó vertiginosamente entre 1986 y 2002 (Annual Percent Change APC 6.2%) y se estabilizó posteriormente. La mortalidad disminuyó desde 1997 en los mayores de 70 años, mientras que en el grupo de 50-69 años fue a partir de 1981. La supervivencia relativa a cinco años fue 69.8% (IC95% 67.5-72.0) y se asoció de manera significativa con la edad, periodo de diagnóstico y estrato socioeconómico. Conclusión. El incremento en la incidencia del CP coincide temporalmente con la implementación del antígeno específico de próstata (PSA por sus siglas en inglés) en Cali; hay evidencia de mejoría en la supervivencia en el CP y disminución en su mortalidad.

Objective. To analyze the trend in prostate cancer survival, incidence and mortality rates in Cali, Colombia from 1962 to 2011. Materials and methods. Based on the Cancer Registry of Cali, Colombia and the mortality registry of the City's Public Health Secretary, incidence, mortality age-standardized rates and relative survival were calculated during 1962-2011. Results. Prostate cancer incidence rates increased sharply between 1986 and 2002 (APC: 6.21%) and then leveled off. Mortality diminished in 1997 in men older than 70 years-old while in men aged 50-69 years declined since 1981. The 5-year-relative-survival was 69.8% (CI95% 67.5-72.0) and it was significantly associated with age, quinquennial period of diagnosis and socioeconomic strata. Conclusion. The increase in incidence rates of prostate cancer in time coincides with the implementation of the PSA in Cali. There is evidence of improvement in prostate cancer survival, and decreased prostate cancer mortality.

Incidencia, mortalidad y supervivencia por cáncer colorrectal en Cali, Colombia, 1962-2012 / Colorectal cancer incidence, mortality and survival in Cali, Colombia, 1962-2012

Objetivo. Estudiar el comportamiento del cáncer colorrectal (CCR) en Cali, Colombia, durante el periodo 1962-2012, utilizando la información del Registro Poblacional de Cáncer de Cali y de la Secretaría de Salud Municipal de Cali. Material y métodos. Análisis ecológico de series de tiempo para estudiar la tendencia de las tasas de incidencia (1962-2007) y mortalidad por CCR (1984-2012); y un análisis de supervivencia de la serie de casos de CCR registrados en Cali entre 1995-2004. La tendencia temporal de las tasas de incidencia (TIEE) y mortalidad (TMEE) estandarizadas por edad se estudió mediante el cambio medio anual (APC por sus siglas en inglés). Se estimó la supervivencia relativa a cinco años y se hizo un análisis múltiple mediante el modelo de regresión de riesgos proporcionales de Cox. Resultados. Durante el periodo 1962-2007, las TIEE de CCR aumentaron en los hombres y mujeres residentes en Cali; APC= 2.6 (IC95% 2.2-3.0) y APC= 2.2% (IC95% 1.8-2.7), respectivamente. Entre 1984-2012 las TMEE permanecieron estables en las mujeres y en los hombres aumentaron en todos los grupos de edad; APC=1.8 (IC95% 0.8-2.8). La supervivencia relativa a cinco años fue independiente del sexo y aumentó de 29.7% en 1995-1999 a 39.8% durante 2000-2004. El riesgo de morir por CCR fue mayor en las personas de estratos socioeconómicos (ESE) bajos frente a los ESE altos, HR= 2.1 (IC95% 1.7-2.6); en los mayores de 70 años frente a los <50, HR= 2.4 (IC95% 1.9-2.9) y en el periodo 1995-1999 frente al 2000-2004 HR=1.5 (IC95% 1.3-1.7). Conclusión. El cáncer de colon y recto está ocupando un lugar preponderante entre los cánceres de mayor importancia en Cali, Colombia.

Objective. To study the colorectal cancer (CRC) behavior in Cali, Colombia, during the 1963-2012 period using data from the Population-based Cancer Registry of Cali and the Municipal Health Secretariat of Cali. Materials and methods. An ecological time series analysis to study the CRC incidence (1962-2007) and mortality (1984-2012) rate trends; and a survival analysis of CRC cases registered in Cali between 1995 and 2004 were conducted. The age-standardized temporal trend of incidence (I-ASR) and mortality (M-ASR) rates were studied using an annual percent change (APC). The 5-year relative survival was estimated and a multivariate analysis was performed using the Cox proportional hazard regression model. Results. During the 1962-2007 period, CRC TTIR increased in men and women living in Cali [APC= 2.6 (95% CI 2.2-3.0) and APC= 2.2% (95% CI 1.8-2.7), respectively]. In the 1984-2012 period, the TTMR remained stable in women but increased in men in all age groups [APC= 1.8 (95% CI 0.8-2.8)]. The 5-year relative survival was independent of sex and increased from 29.7% in 1995-1999 to 39.8% in 2000-2004. The risk of dying from CRC was higher in people of lower socio-economic status (SES) vs higher SES [HR= 2.1 (95% CI: 1.7-2.6)], among people older than 70 years of age vs younger than 50 years [HR= 2.4 (95% CI: 1.9-2.9)], and for the 1995-1999 period vs 2000-2004 period [HR= 1.5 (95% CI 1.3-1.7)]. Conclusion. CRC is beginning to take a prominent place among the most important cancers in Cali, Colombia.

Dieta y cáncer gástrico en México y en el mundo / Diet and gastric cancer in Mexico and in the world

El cáncer gástrico (CG) es la cuarta causa de muerte por cáncer a nivel global. La dieta y el consumo de alcohol y tabaco, además de la infección por Helicobacter pylori determinan un gran número de casos de esta neoplasia. Algunos alimentos contienen sustancias que podrían influir en el proceso de carcinogénesis gástrica, aunque los mecanismos subyacentes no están completamente dilucidados. En México y el mundo, la disminución en el consumo de frutas, vegetales no feculentos y allium, leguminosas y alimentos fuente de selenio, así como el aumento en el consumo de sal, alimentos salados, salmuera y ahumados, chile, carnes procesadas y asadas o a la parrilla se han asociado respectivamente con un aumento de riesgo de CG. Con la evidencia disponible, se podrían desarrollar y evaluar programas para la prevención y control del CG.

Gastric cancer (GC) is the fourt leading cause of cancer death at global level. Diet, alcohol and tobacco, in addition to Helicobacter pylori infection, account for a large number of cases. Some substances contained in foods may influence GC carcinogenesis process; however, the underlying mechanisms have not been fully elucidated. In Mexico and worldwide, a low intake of fruits, non-starchy and allium vegetables, pulses, and foods containing selenium, as well as high intake of salt, salty, salted and smoked foods, chili pepper, processed and grilled/barbecued meats, have been respectively associated with an increased risk of GC. Based on the available evidence, programs for GC prevention and control could be developed and evaluated.