Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer

Aim

This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer.

Background

Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known.

Materials and methods

Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4–81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6–79.2 Gy), respectively.

Results

The time between the last session and the last treatment follow up was a median of 10 months (range, 3–24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones.

Conclusions

RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome.     

Growth response of Pinus densiflora seedlings to different fertilizer compound ratios in a recently burned area in the eastern coast of Korea

This study was conducted to determine fertilizer compound ratios suitable for soil conditions and tree seedling growth in recently burned areas in Korean forests. Currently, the conventional fertilizer ratio applied to undisturbed forests in Korea is N:P:K 3:4:1. In this study, Japanese red pine (Pinus densiflora S. et Z.) seedlings planted in the burned area were fertilized over four growing seasons with the following NPK compound ratios: unfertilized (CON), 3:4:1, 6:4:1, 3:8:1, and 3:4:2. Fertilization generally increased current-year needle nutrient concentrations of the seedlings, and the chlorophyll a:b ratio in CON was significantly lower than in all fertilized plots. Fertilization significantly affected the growth of the pine seedlings, which had 71–87 % more height growth and 29–67 % increased root collar diameter (RCD) compared to CON. The increases in height and RCD were significantly higher with the 6:4:1 and 3:8:1 ratios than with the 3:4:1 ratio. The 3:4:2 and 3:4:1 fertilizer ratios had no effect on the RCD growth of seedlings. This suggests that the early growth of pine seedlings could be improved by providing high N and P supplies to areas affected by forest fires rather than the conventional fertilizer ratio of 3:4:1 in Korean forest soils. Therefore, application of the suitable fertilization ratio may be a very effective way to reduce reforestation cost as well as to shorten restoration period.     

Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8

Alternative splicing plays an important role in gene expression by producing different proteins from a gene. Caspase-2 pre-mRNA produces anti-apoptotic Casp-2S and pro-apoptotic Casp-2L proteins through exon 9 inclusion or skipping. However, the molecular mechanisms of exon 9 splicing are not well understood. Here we show that knockdown of SRSF3 (also known as SRp20) with siRNA induced significant increase of endogenous exon 9 inclusion. In addition, overexpression of SRSF3 promoted exon 9 skipping. Thus we conclude that SRSF3 promotes exon 9 skipping. In order to understand the functional target of SRSF3 on caspase-2 pre-mRNA, we performed substitution and deletion mutagenesis on the potential SRSF3 binding sites that were predicted from previous reports. We demonstrate that substitution mutagenesis of the potential SRSF3 binding site on exon 8 severely disrupted the effects of SRSF3 on exon 9 skipping. Furthermore, with the approach of RNA pulldown and immunoblotting analysis we show that SRSF3 interacts with the potential SRSF3 binding RNA sequence on exon 8 but not with the mutant RNA sequence. In addition, we show that a deletion of 26 nt RNA from 5′ end of exon 8, a 33 nt RNA from 3′ end of exon 10 and a 2225 nt RNA from intron 9 did not compromise the function of SRSF3 on exon 9 splicing. Therefore we conclude that SRSF3 promotes exon 9 skipping of caspase-2 pre-mRNA by interacting with exon 8. Our results reveal a novel mechanism of caspase-2 pre-mRNA splicing.     

Additive Effect between IL-13 Polymorphism and Cesarean Section Delivery/Prenatal Antibiotics Use on Atopic Dermatitis: A Birth Cohort Study (COCOA)

Background

Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy.

Methods

The Cohort for Childhood of Asthma and Allergic Diseases (COCOA) was selected from the general Korean population. A pediatric allergist assessed 412 infants for the presence of AD at 1 year of age. Their cord blood DNA was subjected to interleukin (IL)-13 (rs20541) and cluster-of-differentiation (CD)14 (rs2569190) genotype analysis.

Results

The combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (adjusted odds ratio, 5.70; 95% CI, 1.19–27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. There was a trend of interaction between IL-13 (rs20541) and delivery mode with respect to the subsequent risk of AD. (P for interaction = 0.039) Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had a lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05).

Conclusion

Cesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic predisposition.     

Synergistic Effect of Viral Load and Alcohol Consumption on the Risk of Persistent High-Risk Human Papillomavirus Infection

PurposeThis prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR) human papillomavirus (HPV) infection.MethodsAmong women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI) and synergy index (S) were calculated.ResultsAmong drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05–8.18) and 2-year persistence (OR 8.08, CI 2.36–27.6) were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89–9.05) and 2-year persistence (OR 6.61, CI 2.09–20.9) were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40–6.75 or OR 2.05, CI 0.87–4.83) and 2-year persistence (OR 6.40, CI 1.72–23.8 or OR 4.14, CI 1.18–14.6). The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than on the risk of 1-year persistence (RERI = 1.21, S = 1.63).ConclusionsThe synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load.     

Protein Thermodynamics Can Be Predicted Directly from Biological Growth Rates

Life on Earth is capable of growing from temperatures well below freezing to above the boiling point of water, with some organisms preferring cooler and others hotter conditions. The growth rate of each organism ultimately depends on its intracellular chemical reactions. Here we show that a thermodynamic model based on a single, rate-limiting, enzyme-catalysed reaction accurately describes population growth rates in 230 diverse strains of unicellular and multicellular organisms. Collectively these represent all three domains of life, ranging from psychrophilic to hyperthermophilic, and including the highest temperature so far observed for growth (122°C). The results provide credible estimates of thermodynamic properties of proteins and obtain, purely from organism intrinsic growth rate data, relationships between parameters previously identified experimentally, thus bridging a gap between biochemistry and whole organism biology. We find that growth rates of both unicellular and multicellular life forms can be described by the same temperature dependence model. The model results provide strong support for a single highly-conserved reaction present in the last universal common ancestor (LUCA). This is remarkable in that it means that the growth rate dependence on temperature of unicellular and multicellular life forms that evolved over geological time spans can be explained by the same model.     

Short-Term Effect of Temperature on Daily Emergency Visits for Acute Myocardial Infarction with Threshold Temperatures

Background

The relationship between temperature and myocardial infarction has not been fully explained. In this study, we identified the threshold temperature and examined the relationship between temperature and emergency admissions due to MI in Korea.

Methods

Poisson generalized additive model analyses were used to assess the short-term effects of temperature (mean, maximum, minimum, diurnal) on MI emergency visits, after controlling for meteorological variable and air pollution (PM10, NO₂). We defined the threshold temperature when the inflection point showed a statistically significant difference in the regression coefficients of the generalized additive models (GAMs) analysis. The analysis was performed on the following subgroups: geographical region, gender, age (<75 years or ≥75 years), and MI status (STEMI or non-STEMI).

Results

The threshold temperatures during heat exposure were for the maximum temperature as 25.5–31.5°C and for the mean temperature as 27.5–28.5°C. The threshold temperatures during cold exposure were for the minimum temperature as −2.5–1.5°C. Relative risks (RRs) of emergency visits above hot temperature thresholds ranged from 1.02 to 1.30 and those below cold temperature thresholds ranged from 1.01 to 1.05. We also observed increased RRs ranged from 1.02 to 1.65 of emergency visits when temperatures changes on a single day or on successive days.

Conclusions

We found a relationship between temperature and MI occurrence during both heat and cold exposure at the threshold temperature. Diurnal temperature or temperature change on successive days also increased MI risk.