Robustness of hypofractionated breast radiotherapy after breast-conserving surgery with free breathing.

Purpose: This study aimed to evaluate the robustness with respect to the positional variations of five planning strategies in free-breathing breast hypofractionated radiotherapy (HFRT) for patients after breast-conserving surgery. Methods: Twenty patients who received breast HFRT with 42.72 Gy in 16 fractions were retrospectively analyzed. Five treatment planning strategies were utilized for each patient, including 1) intensity-modulated radiation therapy (IMRT) planning (IMRTpure); 2) IMRT planning with skin flash tool extending and filling the fluence outside the skin by 2 cm (IMRTflash); 3) IMRT planning with planning target volume (PTV) extended outside the skin by 2 cm in the computed tomography dataset (IMRTePTV); 4) hybrid planning, i.e., 2 Gy/fraction three-dimensional conformal radiation therapy combined with 0.67 Gy/fraction IMRT (IMRThybrid); and 5) hybrid planning with skin flash (IMRThybrid-flash). All plans were normalized to 95% PTV receiving 100% of the prescription dose. Six additional plans were created with different isocenter shifts for each plan, which were 1 mm, 2 mm, 3 mm, 5 mm, 7 mm, and 10 mm distally in the X (left-right) and Y (anterior-posterior) directions, namely, (X,Y), to assess their robustness, and the corresponding doses were recalculated. Variation of dosimetric parameters with increasing isocenter shift was evaluated. Results: All plans were clinically acceptable. In terms of robustness to isocenter shifts, the five planning strategies followed the pattern IMRTePTV, IMRThybrid-flash, IMRTflash, IMRThybrid, and IMRTpure in descending order. V 95% of IMRTePTV maintained at 99.6% ± 0.3% with a (5,5) shift, which further reduced to 98.2% ± 2.0% with a (10,10) shift. IMRThybrid-flash yielded the robustness second to IMRTePTV with less risk from dose hotspots, and the corresponding V 95% maintained >95% up until (5,5). Conclusion: Considering the dosimetric distribution and robustness in breast radiotherapy, IMRTePTV performed best at maintaining high target coverage with increasing isocenter shift, while IMRThybrid-flash would be adequate with positional uncertainty<5 mm.

Effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung VMAT SBRT with 6 MV FFF beam.

PURPOSE: The purpose of this study is to investigate the effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung stereotactic body radiation therapy (SBRT) using volumetric modulated arc therapy (VMAT) with 6 MV flattening-filter-free (FFF) beam. METHODS: Twenty patients with early stage non-small cell lung cancer were included. For each patient, high-complexity (HC) and low-complexity (LC) three-partial-arc VMAT plans were optimized by adjusting the normal tissue objectives and the maximum monitoring units (MUs) for a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) using 6 MV FFF beam. The effect of plan complexity was comprehensively evaluated in three aspects: (1) The dosimetric parameters, including CI, D2cm, R50, and dose-volume parameters of organs at risk were compared. (2) The delivery accuracy was assessed by pretreatment quality assurance for two groups of plans. (3) The motion-induced dose deviation was evaluated based on point dose measurements near the tumor center by using a programmable phantom. The standard deviation (SD) and maximum dose difference of five measurements were used to quantify the interplay effect. RESULTS: The dosimetry of HC and LC plans were similar except the CI (1.003 ± 0.032 and 1.026 ± 0.043, p = 0.030) and Dmax to the spinal cord (10.6 ± 3.2 and 9.9 ± 3.0, p = 0.012). The gamma passing rates were significantly higher in LC plans for all arcs (p < 0.001). The SDs of HC and LC plans ranged from 0.5-16.6% and 0.03-2.9%, respectively, under the conditions of one-field, two-field, and three-field delivery for each plan with 0.5, 1, 2, and 3 cm motion amplitudes. The maximum dose differences of HC and LC plans were 34.5% and 9.1%, respectively. CONCLUSION: For lung VMAT SBRT, LC plans have a higher delivery accuracy and a lower motion-induced dose deviation with similar dosimetry compared with HC plans.

Selection Strategy of Jaw Tracking in VMAT Planning for Lung SBRT.

PURPOSE: This study aimed to investigate the dosimetric effect and delivery reliability of jaw tracking (JT) with increasing planning target volume (PTV) for lung stereotactic body radiation therapy (SBRT) plans. A threshold of PTV was proposed as a selection criterion between JT and fixed-jaw (FJ) techniques. METHODS: A total of 28 patients with early-stage non-small-cell lung cancer were retrospectively included. The PTVs ranged from 4.88 cc to 68.74 cc, prescribed with 48 Gy in four fractions. Three-partial-arc volumetric modulated arc therapy (VMAT) plans with FJ and with JT were created for each patient with the same optimization objectives. These two sets of plans were compared using metrics, including conformity index (CI), V50%, R50%, D2cm, dose-volume parameters of organs at risk, and monitor units (MUs). The ratio of small subfields (<3 cm in either dimension), %SS, was acquired as a surrogate for the small-field uncertainty. Statistical analyses were performed to evaluate the correlation between the differences in these parameters and the PTV. RESULTS: The V50%, R50%, D2cm, and V20Gy, D1,500cc, and D1,000cc of the lung showed a statistically significant improvement in JT plans as opposed to FJ plans, while the number of MU in JT plans was higher by an average of 1.9%. Between FJ and JT plans, the PTV was strongly correlated with the differences in V50%, moderately correlated with those in V20Gy of the lung, and weakly correlated with those in D2cm and D1,500cc of the lung. By using JT, %SS was found to be negatively correlated with the PTV, and the PTV should be at least approximately 12.5 cc for an expected %SS <50%, which was 15 cc for a %SS <20% and 20 cc for a %SS <5%. CONCLUSIONS: Considering the dosimetric differences and small-field uncertainties, JT could be selected using a PTV threshold, such as 12.5, 15, or 20 cc, on the basis of the demand of delivery reliability for lung SBRT.

Systematic quantitative evaluation of Plan-IQ for intensity-modulated radiation therapy after modified radical mastectomy.

Radiotherapy (RT) is one of the main treatment strategies of breast cancer. It is challenging to design RT plans that can completely cover the target area while protecting organs at risk (OAR). The Plan-IQ feasibility tool can estimate the best sparing dose of OAR before optimizing the Plan. A systematic quantitative evaluation of the quality change of intensity-modulated radiation therapy (IMRT) using the Plan-IQ feasibility tool was performed for modified radical mastectomy in this study. We selected 50 patients with breast cancer treated with IMRT. All patients received the same dose in the planning target volume (PTV). The plans are categorized into two groups, with each patient having one plan in each group: the clinically accepted normal plan group (NP group) and the repeat plan group (RP group). An automated planning strategy was generated using a Plan-IQ feasibility dose volume histogram (FDVH) in RP group. These plans were assessed according to the dosimetry parameters. A detailed scoring strategy was based on the RTOG9804 report and 2018 National Comprehensive Cancer Network guidelines, combined with clinical experience. PTV coverage in both groups was achieved at 100% of the prescribed dose. Except for the thyroid coverage, the dose limit of organs at risk (OAR) in RP group was significantly better than that in NP group. In the scoring analysis, the total scores of RP group decreased compared to that of NP group (P < 0.05), and the individual scores of PTV and OAR significantly changed. PTV scores in RP group decreased (P < 0.01); however, OAR scores improved (P < 0.01). The Plan-IQ FDVH was useful for evaluating a class solution for IMRT planning. Plan-IQ can automatically help physicians design the best OAR protection plan, which sacrifices part of PTV, but still meets clinical requirements.

Optimization of collimator angles in dual-arc volumetric modulated arc therapy planning for whole-brain radiotherapy with hippocampus and inner ear sparing.

To optimize the collimator angles in dual-arc volumetric modulated arc therapy (VMAT) plans for whole-brain radiotherapy with hippocampus and inner ear sparing (HIS-WBRT). Two sets of dual-arc VMAT plans were generated for 13 small-cell lung cancer patients: (1) The collimator angles of arcs 1 and 2 (θ1/θ2) were 350°/10°, 350°/30°, 350°/45°, 350°/60°, and 350°/80°, i.e., the intersection angle of θ1 and θ2 (Δθ) increased. (2) θ1/θ2 were 280°/10°, 300°/30°, 315°/45°, 330°/60°, and 350°/80°, i.e., Δθ = 90°. The conformity index (CI), homogeneity index (HI), monitor units (MUs), and dosimetric parameters of organs-at-risk were analyzed. Quality assurance for Δθ = 90° plans was performed. With Δθ increasing towards 90°, a significant improvement was observed for most parameters. In 350°/80° plans compared with 350°/10° ones, CI and HI were improved by 1.1% and 25.2%, respectively; MUs were reduced by 16.2%; minimum, maximum, and mean doses (D100%, Dmax, and Dmean, respectively) to the hippocampus were reduced by 5.5%, 6.3%, and 5.4%, respectively; Dmean to the inner ear and eye were reduced by 0.7% and 5.1%, respectively. With Δθ kept at 90°, the plan quality was not significantly affected by θ1/θ2 combinations. The gamma-index passing rates in 280°/10° and 350°/80° plans were relatively lower compared with the other Δθ = 90° plans. Δθ showed a significant effect on dual-arc VMAT plans for HIS-WBRT. With Δθ approaching 90°, the plan quality exhibited a nearly continuous improvement, whereas with Δθ = 90°, the effect of θ1/θ2 combination was insignificant.

Haplotype analysis on correlation between transcription factor 7-like 2 gene polymorphism and breast cancer risk.

BACKGROUND: Up to now, limited researches focused on the association between transcription factor 7-like 2 gene (TF7L2) gene single nucleotide polymorphisms (SNPs) and breast cancer (BC) risk. The aim of this study was to evaluate the associations between TF7L2 and BC risk in Chinese Han population. METHODS: Logistic regression model was used to test the correlation between polymorphisms and BC risk. Strength of association was evaluated by odds ratio (OR) and 95% confidence interval (CI). Generalized multifactor dimensionality reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interaction. RESULTS: Logistic regression analysis indicated that the BC risk was obviously higher in carriers of rs1225404 polymorphism C allele than that in TT genotype carriers (TC or CC versus TT), adjusted OR (95%CI) =1.40 (1.09-1.72). Additionally, we also discovered that people with rs7903146- T allele had an obviously higher risk of BC than people with CC allele (CT or TT versus CC), adjusted OR (95%CI) =1.44 (1.09-1.82). GMDR model was used to research the effect of interaction among 4 SNPs and environmental factors on BC risk. We discovered an important two-locus model (p = 0.0100) including rs1225404 and abdominal obesity, suggesting a potential gene-environment correlation between rs1225404 and abdominal obesity. In general, the cross-validation consistency of two-locus model was 10 of 10, and the testing accuracy was 0.632. Compared with subjects with normal waist circumference (WC) value and rs1225404 TT genotype, abdominal obese subjects with rs1225404 TC or CC genotype had the highest BC risk. After covariate adjustment, OR (95%CI) was 2.23 (1.62-2.89). Haplotype analysis indicated that haplotype containing rs1225404-T and rs7903146-C alleles were associated with higher BC risk. CONCLUSIONS: C allele of rs1225404 and T allele of rs7903146, interaction between rs1225404 and abdominal obesity, rs1225404-T and rs7903146-C haplotype were all related to increased BC risk.

Technical Note: Induced radioactivity in stereotactic body radiation therapy with a flattening-filter-free 10 MV beam model.

PURPOSE: The induced radioactivity in stereotactic body radiation therapy with a flattening-filter-free 10 MV beam model (10 FFF SBRT) was investigated for the risk to therapists. METHODS: This study was performed on a Varian TrueBeam linac. The induced radioisotopes were identified by γ spectroscopy. The dose rate from the induced activity was measured for 12 treatment cycles in 4 h continuously. The impacts of the characteristic factors of 10 FFF SBRT on the dose rate were investigated, including monitor units (MU), beam rate, field size, and flattening filter. The dose rate was compared between the SBRT plans and conventional fractionation plans. A mathematical model was used to analyze the results and estimate the annual dose to therapists. RESULTS: (a) The induced radioisotopes included 24 Na, 28 Al, 38 Cl, 56 Mn, 66 Cu, 187 W, and 196 Au. (b) In 4 h, the total dose contribution ratios were more than 70% for 28 Al, about 20% for 56 Mn, and 10% for all other long-lived radioisotopes, combining doses at the isocenter and end of the treatment couch. (c) The dose rate showed a nonlinear growth with increasing MU and beam rate. The variation of the dose rate was complicated with the jaw field and not sensitive to the MLC field. The removal of the flattening filter reduced the dose rate by about 40%. The dose level of SBRT was two to three times that of conventional fractionation. (d) The estimated annual dose to therapists was up to 0.20 mSv/y. CONCLUSIONS: The induced radioactivity in 10 FFF SBRT was higher compared with that in 10 MV conventional fractionation. More MU and higher beam rate were the primary factors that caused the increase. The therapists should wait longer after beam-off to reduce the occupational dose. In addition, aluminum and manganese should be less used in the treatment room.

Transplantation of neural stem cells encapsulated in hydrogels improve functional recovery in a cauda equina lesion model.

This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model. NSCs were isolated from neonatal dorsal root ganglion (nDRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test. NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo. Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina. Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.

Application of auto-planning in radiotherapy for breast cancer after breast-conserving surgery.

To evaluate the quality of planning target volume (PTV) and organs at risk (OAR) generated by the manual Pinnacle planning (manP) and Auto-Planning (AP) modules and discuss the feasibility of AP in the application of radiotherapy for patients with breast cancer. Thirty patients who underwent breast-conserving therapy were randomly selected. The Philips Pinnacle 9.10 treatment planning system was used to design the manP and AP modules for PTV and OAR distribution on the same computed tomography. A physician compared the plans in terms of dosimetric parameters and monitor units (MUs) using blind qualitative scoring. Statistical differences were evaluated using paired two-sided Wilcoxon's signed-rank test. On comparing the plans of AP and manP modules, the conformal index (P < 0.01) and D50 (P = 0.04) of PTV in the AP group was lower than those in the manP group, while D1 was higher (P = 0.03). In terms of dosimetry of OAR, ipsilateral lung V20 Gy (P < 0.01), V10 Gy (P < 0.01), V5 Gy (P < 0.05), and Dmean (P < 0.01) of the AP group were better than those of the manP group. Heart V40 Gy and Dmean of all patients with breast cancer in the AP group were lower than those in the manP group (P < 0.01). Moreover, 12 patients with left breast cancer had the same results (P < 0.01). The MU value of the intensity-modulated radiation therapy module designed using two different methods was higher in the AP group than in the manP group (P = 0.32), although there was no statistical significance. The AP module almost had an equal quality of PTV and dose distribution as the manP module, and its OAR was less irradiated.

MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest.

BACKGROUND: Paclitaxel (PTX) resistance is a main obstacle for the treatment of triple-negative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells. METHODS: Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally. RESULTS: In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model. CONCLUSION: We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR­153-5p may be a promising agent for patients with PTX-resistant TNBC.

The benefits of expressive writing among newly diagnosed mainland Chinese breast cancer patients.

The study aimed to evaluate the effects of an expressive writing intervention on quality of life (QoL) among mainland Chinese breast cancer patients. A total of 118 Chinese breast cancer patients were randomly assigned to one of four groups: a cancer-facts writing condition (CTL group), an emotional disclosure writing condition (EMO group), a self-regulation writing condition (SR group), or a neutral control condition with no writing tasks (CON group). QoL was assessed by FACT-B at baseline, 3-, and 6-month follow-ups. A repeated measure analysis of variance revealed significant effects of time (F = 13.9, P < 0.001, η2 = 0.20) and the time × group interaction (F = 3.5, P < 0.01, η2 = 0.08) on QoL. Residualized change models showed that the CTL, EMO and SR groups reported higher levels of QoL than the CON group at the 6-month follow-up. The EMO group had a higher level of QoL than the SR group. The CTL group had higher level of physical well-being compared to the SR group. Mainland Chinese breast cancer patients shortly after diagnosis benefit from expressive writing. They benefited more from cancer-facts and emotional disclosure compared to self-regulation. The study indicated that the impact of expressive writing may differ due to stage of cancer survivorship, social, and cultural context.

The detrimental effects of ambivalence over emotional expression on well-being among Mainland Chinese breast cancer patients: Mediating role of perceived social support.

OBJECTIVE: Recent research has documented the harmful effects of ambivalence over emotional expression (AEE) on psychological well-being, but few studies to date have examined AEE among Mainland Chinese breast cancer patients, an ethnic group that prioritizes emotion restraint to preserve social harmony. The present study examined the relationship between AEE and well-being (viz, anxious and depressive symptoms and quality of life) and evaluated perceived social support as a potential mediator of this relationship in a sample of Mainland Chinese breast cancer patients. METHODS: Three hundred twenty-seven Chinese breast cancer patients recruited from Weifang, China, completed a self-reported questionnaire containing the Ambivalence over Emotional Expression Questionnaire (AEQ), the Medical Outcomes Study Social Support Scale (MOS-SSS), the Self-rating Anxiety Scale (SAS), the Self-rating Depression Scale (SDS), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). RESULTS: Overall, Mainland Chinese breast cancer patients endorsed high levels of AEE. A series of mediation analyses revealed perceived social support served as a partial mediator of the relationship between AEE and well-being. Specifically, AEE was associated with lower perceived social support (ßs = -.13, P < .001), which in turn, was associated with greater anxious symptoms (ß = .23, P < .001), depressive symptoms (ß = .20, P < .001) and lower quality of life (ß = -.30, P < .001). CONCLUSIONS: The harmful relationship between AEE and well-being is partially explained by reduced social support. Psychosocial interventions that facilitate emotional disclosure without harming social harmony may be culturally effective for mainland Chinese breast cancer patients.

Limited variations in susceptibility to an insecticidal double-stranded RNA (dsvATPaseE) among a laboratory strain and seven genetically differentiated field populations of Tribolium castaneum.

There has been a considerable growth in interest to use RNA interference (RNAi) as a novel insect pest management strategy in the past 10 years. However, there has been virtually no information on insect population variations in response to double-stranded RNA (dsRNA) molecules. The objective of this study was to generate baseline susceptibilities of the red flour beetle (Tribolium castaneum) to an insecticidal dsRNA targeting vacuolar H+-ATPase subunit E gene (dsvATPaseE), and correlate the susceptibility data with sequence and expression variations of the target gene (vATPaseE), expression variations of the RNAi core genes, and overall genetic differences among a laboratory strain and seven geographical field populations of T. castaneum collected in China. Our results showed limited variations in the LD50 values of dsvATPaseE, which ranged from 0.10 to 0.29 ng/larva among the laboratory strain and the seven field populations. Considering the overlapping of the 95% confidence intervals of their LD50 values, there were no significant differences among the laboratory strain and field populations. We also found limited sequence polymorphisms and low frequencies of the polymorphisms of vATPaseE, and limited variations (<2-fold) of the endogenous expression of vATPaseE among the laboratory strain and field populations. However, we found considerable genetic variations among the individuals within each field population for most of eight loci and moderate to large genetic variations among the field populations. These results demonstrated that although the genetic variabilities were considerable among these field populations, the efficiency of RNAi targeting vATPaseE was highly consistent in T. castaneum. Our study provides work frames of resistance risk assessment for RNAi-based insect pest management programs.

Association of BCSC-1 and MMP-14 with human breast cancer.

Breast cancer suppressor candidate-1 (BCSC-1) is a candidate tumor suppressor gene that was identified recently. Decreased levels of BCSC-1 have been detected in a variety of cancer types in previous studies. Matrix metalloproteinase (MMP)-14 is a membrane-type MMP that plays an important role in tumor progression and prognosis. Previous research has indicated that MMP-14 is highly expressed in different cancer types and promotes tumor invasion or metastasis by remodeling the extracellular matrix. However, there have been few reports on BCSC-1 and MMP-14 in human breast cancer in recent years. In the present study, the association of BCSC-1 and MMP-14 with human breast cancer was investigated. The immunohistochemical analysis results revealed reduced expression of BCSC-1 and overexpression of MMP-14 in breast cancer tissues compared with adjacent normal breast tissues. Quantitative polymerase chain reaction and western blot analyses also showed that BCSC-1 was expressed at significantly lower levels, and that MMP-14 was expressed at significantly higher levels in breast cancer tissues compared with healthy breast tissue. Furthermore, decreased expression of BCSC-1 and overexpression of MMP-14 were associated with tumor cellular differentiation, lymph node metastasis and distant metastasis. A correlational analysis between BCSC-1 and MMP-14 was also conducted, and the results indicated a negative correlation between the two. In conclusion, the current findings indicate that BCSC-1 is downregulated, while MMP-14 is overexpressed in human breast cancer. These two genes may play important roles during the process of human breast cancer development.

N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors.

The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32-35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR.

Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide modified nanocarriers.

CONTEXT: Breast cancer is the most common cancer in female population. Breast cancer chemotherapy using doxorubicin (DOX) is well illustrated. However, a significant obstacle for successful chemotherapy with DOX is multidrug resistant (MDR) in breast cancer cells. Targeted nanocarriers have emerged as frontier research for the improvement of cancer chemotherapy. OBJECTIVE: Bombesin (Bn)-modified, DOX-loaded solid lipid nanoparticles (Bn-DOX/SLNs) were constructed. Doxorubicin-resistant MCF-7/MDR human breast cancer cells and the cancer animal models were applied for the evaluation of the in vitro and in vivo anti-tumor effect of Bn-DOX/SLNs. METHODS: Bn-conjugated lipids were synthesized. DOX was then loaded into Bn-modified SLNs. The physicochemical properties of the Bn-DOX/SLNs were investigated by particle size and zeta potential measurement, drug loading and drug-entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against MCF-7/MDR cells was investigated, and in vivo anti-tumor of SLNs was evaluated in human breast cancer mice models. RESULTS: Bn-DOX/SLNs showed an excellent in vitro cytotoxicity and in vivo anti-tumor effect both in MCF-7/MDR breast cancer cells and breast cancer animal model. CONCLUSION: The results demonstrated that Bn-DOX/SLNs reversed the resistance of doxorubicin, suggesting that chemotherapy using this kind of targeted nanocarriers may benefit human breast MDR cancer therapy.

Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction.

The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty­four hours after surgery, the rats were divided into low­dose, high­dose, control and sham surgery groups (n=8 per group). The low­ and high­dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post­treatment. Twenty­four hours post­surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST­treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low­ and high­dose groups was noted, however, an increase in the bFGF expression levels was detected in the high­dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST­treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST­induced increase in angiogenesis in rat models of MI.

Dosimetric comparative study of 3 different postoperative radiotherapy techniques (3D-CRT, IMRT, and RapidArc) for II-III stage rectal cancer.

Postoperative radiotherapy is critical for reducing local relapse for advanced rectal carcinoma but has many side effects. Our study compared the dose distribution of target volumes, protection of normal organs at risk (OAR), and monitor unit (MU) for 3 radiotherapy techniques (3-dimensional conformal radiation therapy [3D-CRT], intensity-modulated radiation therapy [IMRT], and RapidArc (Varian Medical Systems, Inc., Palo Alto, CA, USA)). The results advocate for the clinical application of RapidArc technique in the future.Thirty postoperative patients with rectal cancer were enrolled. The 3 radiotherapy plans mentioned above were designed for each patient. The target volume coverage indicators included average dose, conformity index (CI), and homogeneity index (HI) of planning tumor volume (PTV). OAR included the bladder, small intestine, colon, and bilateral proximal femurs. The 30 patients were divided into 3 groups (10 cases in each group) for postoperative radiotherapy with the 3D-CRT, IMRT, or RapidArc technique, respectively.Both the IMRT and RapidArc plans have a significantly higher average PTV dose and better CI and HI (P < 0.01) than 3D-CRT. IMRT and RapidArc result in significantly lower doses of irradiation for all the OAR examined. Both the IMRT and RapidArc plans have a significantly lower V40 of the bladder, small intestine, and colon than 3D-CRT (P < 0.01). The IMRT and RapidArc plans can also reduce the maximum dose (Dmax) for the left proximal femur, V30, and V40 of bilateral proximal femurs compared with 3D-CRT (P < 0.01). Compared with IMRT, RapidArc can further reduce the Dmax of the small intestine, the Dmax and V30 of the bilateral proximal femurs, and the V40 of the right proximal femur (P < 0.01). RapidArc reduces MU remarkably compared with IMRT (P < 0.01). Regarding acute side effects, IMRT and RapidArc can greatly reduce the incidence of grade 3 radiation-induced cystitis and grade 2 enteritis.Both IMRT and RapidArc are better than 3D-CRT regarding PTV coverage and OAR protection. Furthermore, RapidArc is superior to IMRT regarding protection of the small intestine and bilateral proximal femurs and requires a reduced treatment time. RapidArc could be widely applied for postoperative radiotherapy for patients with ΙΙ-ΙΙΙ stage rectal cancer.

NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure.

The neuronal RNA binding protein NOVA regulates splicing, shuttles to the cytoplasm, and co-localizes with target transcripts in dendrites, suggesting links between splicing and local translation. Here we identified >200 transcripts showing NOVA-dependent changes in abundance, but, surprisingly, HITS-CLIP revealed NOVA binds these RNAs in introns rather than 3' UTRs. This led us to discover NOVA-regulated splicing of cryptic exons within these introns. These exons triggered nonsense mediated decay (NMD), as UPF1 and protein synthesis were required for NOVA's effect on RNA levels. Their regulation was dynamic and physiologically relevant. The NMD exons were regulated by seizures, which also induced changes in Nova subcellular localization and mediated large changes in synaptic proteins, including proteins implicated in familial epilepsy. Moreover, Nova haploinsufficient mice had spontaneous epilepsy. The data reveal a hidden means of dynamic RNA regulation linking electrical activity to splicing and protein output, and of mediating homeostatic excitation/inhibition balance in neurons.DOI:http://dx.doi.org/10.7554/eLife.00178.001.