Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage.

Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.

Cytotoxic polyprenylated phloroglucinol derivatives from Hypericum elodeoides Choisy modulating the transactivation of RXRα.

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed.

Cancer risk assessment in modern radiotherapy workflow with medical big data.

Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose-response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI.

Dosimetric comparison of helical tomotherapy, VMAT, fixed-field IMRT and 3D-conformal radiotherapy for stage I-II nasal natural killer T-cell lymphoma.

BACKGROUND: The aim of this study was to compare radiotherapy plans for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL) using helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), Fixed-Field intensity-modulated radiotherapy (IMRT), and three-dimensional conformal radiotherapy (3D-CRT). METHODS: Eight patents with Stage I-II NNKTL treated with IMRT were re-planned for HT, VMAT (two full arcs), and 3D-CRT. The quality of target coverage, the exposure of normal tissue and the efficiency of radiation delivery were analyzed. RESULTS: HT showed significant improvement over IMRT in terms of D98%, cold spot volume and homogeneity index (HI) of planning target volume (PTV). VMAT provided best dose uniformity (p = 0.000) to PTV, while HT had best dose homogeneity among the four radiotherapy techniques (p = 0.000) to PTV. VMAT obviously reduced treatment time (p = 0.010; 0.000) compared to HT and IMRT. Mean dose of left and right optic nerve was significantly reduced by IMRT compared to HT (19.86%, p = 0.000; 21.40%, p = 0.002) and VMAT (8.97%, p = 0.002; 9.35%, p = 0.001), and maximum dose of left lens of VMAT increased over the HT (36.25%, p = 0.043) and IMRT (40.65%, p = 0.001). CONCLUSION: The unexpected results show that both HT and VMAT can achieve higher conformal treatment plans while getting worse organs at risk (OARs) sparing than IMRT for patients with Stage I-II NNKTL. VMAT requires the shortest delivery time, and IMRT delivers the lowest dose to most OARs. The results could provide guidance for selecting proper radiation technologies for different cases.

Estimating nicotine consumption in eight cities using sewage epidemiology based on ammonia nitrogen equivalent population.

Sewage epidemiology is a real-time tool used to monitor tobacco consumption. In this study, we investigated the tobacco consumption in eight cities in Jilin province using sewage epidemiology. We collected influent wastewater samples from ten wastewater treatment plants (WWTPs) that serve nearly four million people. Mean nicotine (NIC) loads ranged from 1.42 to 14.2mg/d/capita, whereas mean cotinine (COT) loads showed lower levels with 0.33 to 2.15mg/d/capita. Population size was estimated to provide an accurate and real-time population based on ammonia nitrogen (NH4-N) concentration in influent. To verify the NH4-N equivalent population, we compared these results with the corresponding population estimated based on the expert knowledge of the local WWTPs operators. Daily consumption of NIC was estimated to be approximately 2.39±1.47mg/d/capita. Monte Carlo simulation was used to analyze uncertainty and variability in the number of cigarettes consumed by smokers in the range of 9.8 to 31.4 per day with a median of 16.9. The data of tobacco consumption in this study coordinated strongly with a traditional survey on the consumption of tobacco in China, indicating sewage epidemiology with NH4-N equivalent population estimation may provide a suitable and useful tool for tobacco use monitoring.

Overexpression of miR­214 promotes the progression of human osteosarcoma by regulating the Wnt/ß­catenin signaling pathway.

The aberrant expression of microRNA (miR)­214 contributes to the regulation of normal and cancer cell biology, and is associated with human malignancies, however, it can operate in a contradictory manner. The role of miR­214 in osteosarcoma remains to be fully elucidated. The aim of the present study was to investigate the effects of miR­214 on osteosarcoma progression and tumor cell proliferation, and examine the molecular mechanism underlying osteosarcoma. The level of miR­214 was determined using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis in osteosarcoma and matched paracancerous tissues, and in human osteosarcoma cancer cell lines. The roles of miR­214 in cell proliferation, survival and cell cycle were analyzed using miR­214 lentivirus (LV­miR­214)­infected osteosarcoma cells. In addition, the downstream target proteins in the Wnt/ß­catenin signaling pathway were evaluated using western blot analysis in the LV­miR­214­infected cells. The LV­miR­214­infected MG63 cells were also treated with exogenous ß­catenin for 24, 48 and 72 h, respectively, following which the expression of ß­catenin was measured using western blot analysis and survival was determined using a 3­(4,5­cimethylthiazol­2­yl)­2,5­diphenyl tetrazolium bromide (MTT) assay. The results of the RT­qPCR analysis showed that the expression level of miR­214 was significantly higher in the osteosarcoma tissues, compared with that in the matched paracancerous tissues, and the same was observed in the osteosarcoma cell lines. The MG63, Saos­2 and U2OS cells were infected with the hsa­mir­214 lentivirus for 48 h, and the levels of miR­214 were significantly upregulated in the human osteosarcoma cancer cells. The overexpression of miR­214 in the MG­63 and Saos­2 cells promoted cell growth, and treatment of the cells with specific antisense­microRNA oligonucleotides (AMOs) for miR­214 for indicated durations reversed the effects of miR­214. Additionally, the AMO­treated MG63 cells showed G0/G1 phase arrest, suggesting that miR­214 contributed to regulation of the cell cycle. In addition, the results of western blot analysis showed that, in the miR­214 lentivirus­infected cells, the levels of cyclin­D1, c­myc and lymphoid enhancer­binding factor­1 were significantly increased, compared with those in the control lentivirus­infected cancer cells. Of note, infection with the miR­214 lentivirus did not affect the levels of Wnt1, Wnt2, Wnt4, Axin or glycogen synthase kinase ß in the U2OS cells, whereas the expression levels of ß­catenin in the MG63 cells and Saos­2 cells were significantly increased. The addition of exogenous ß­catenin effectively reversed the efficiency of miR­214­specific AMOs, which was detected using an MTT assay. These data suggested the critical role of miR­214 in human osteosarcoma via regulation of the Wnt/ß­catenin signaling pathway and demonstrated that miR­214 is as an oncogene for human osteosarcoma.

[Establishment of a Xenografted Acute Myeloid Leukemia Model by using Zebrafish].

Objectve: To investigate the feasibility of establishing xenografted leukemia model by zebrafish, so as to provide the more direct model in vitro and experimental evidence for study of acute myeloid leukemia and screening of the drugs for targeting therapy. METHODS: Acute myeloid leukemia cell line KG-1a was labeled with red fluorescent dye-MitoRed, then the labeled cells were injected into the yolk sac of zebrafish embryos. Morphological observation, cell count and histopathological detection were used to analyse the infiltration and metastasis of KG-1a cells in zebrafish. RESULTS: KG1a cells could proliferate and gradually spread to the entire abdominal cavity of the zebrafish after KG-1a cells were injected into the yolk sac during 1-7, the results of cell counting in vitro also proved a significant proliferation of KG-1a cells in zebrafish, suggesting that the implanted leukemia stem cells could survive, proliferate and spread in zebrafish. Further study showed that the implanted cells could be transfered to the liver of zebrafish, these cells displayed the signature of KG-1a cells by hematoxylin-eosin(HE) staining. CONCLUSIONS: Human acute myeloid leukemia cells KG1a can survive, proliferate and migrate in zebrafish, suggesting xenografted leukemia model of zebrafish has been successfully established. This model may be benefitcial for the study of acute myeloid leukemia and the screening of the drugs for targeting therapy of acute myeloid leukemia.

A parameterized model for mean urinary inflow rate and its preliminary application in radiotherapy for cervical cancer.

Forty-nine patients with stage IIb cervical cancer were included to investigate the changes in bladder volume in response to different approaches to maintaining consistent bladder filling. The impacts of age (P age), water consumption (P wat ), and body mass index (BMI, P bmi ) on the mean urinary inflow rate (v tot ) were analysed. The bladder volume (BV) increased linearly over time. A large variation in v tot among individuals was observed, ranging from 0.19 to 5.13 ml/min. The v tot was correlated with P age (R = -0.53, p = 0.01) and P wat (R = 0.84, p = 0.00), and no correlation between v tot and P bmi was found (p > 0.05). Therefore, v tot could be parameterized using two methods: multivariable linear regression and iterative fitting. There was no statistically significant difference between the two methods. The model accuracy was successfully assessed with several validation tests for patients with good compliance (79.2% of all patients), and the proportion of radiotherapy (RT) fractions with zero wait time (one ultrasound (US) scan) increased from 6.5% to 41.2%. The optimal US scanning number and RT time could be provided using this model. This adaptive RT approach could reduce patient discomfort caused by holding onto urine and reduce technician labour as well as cost.

A comparison of volumetric modulated arc therapy and sliding-window intensity-modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell lymphoma.

This article is aimed to compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed dose of the planning target volume (PTV) was 50Gy in 25 fractions. The VMAT plans with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an Eclipse treatment planning system; the monitor units (MUs) and treatment time (T) were scored to measure the expected treatment efficiency. All the 10 patients under the study were subject to comparisons regarding the quality of target coverage, the efficiency of delivery, and the exposure of normal adjacent organs at risk (OARs). The study shows that VMAT was associated with a better conformal index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to OARs than IMRT. The MUs with VMAT (650.80 ± 24.59) were fewer than with IMRT (1300.10 ± 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose fractions. The treatment time with VMAT (3.20 ± 0.02 minutes) was shorter than with IMRT (7.38 ± 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We found that VMAT and IMRT both provide satisfactory target dosimetric coverage and OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in comparison with IMRT, is still a better choice for treatment of patients with Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter delivery time.

Imaging appearance of a singular metastatic adenoid cystic carcinoma of the right kidney: A case report and literature review.

Renal metastasis of a submandibular gland adenoid cystic carcinoma is clinically rare when it presents with an atypical imaging appearance of singular renal metastases. Whole-body positron emission tomography (PET)/computed tomography (CT) can determine whether the singular renal mass is benign or malignant and identify metastases in other parts of the body, particularly in uncommon sites. In the present case, the patient developed a rare partial metastasis to the right kidney three years after undergoing a surgery for submandibular gland adenoid cystic carcinoma. Based on the present case, whole-body PET/CT examination could provide an important basis for making treatment plans for singular renal metastases.

The value of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the detection and characterization of soft tissue metastasis.

Metastatic tumours presenting as soft tissue metastasis (STM) are relatively rare. STM represents metastasis to the muscle and subcutaneous tissues. The majority of the currently available clinical or radiological data on STM consist of isolated case reports or reviews. The aim of this study was to report the manifestations, origin and distribution of STM detected by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and to assess the value of 18F-FDG PET/CT in the characterisation of STM. We reviewed 17 cases of patients with STM who underwent 18F-FDG PET/CT scanning. The imaging and clinical data of these patients were retrospectively analysed. This method is very sensitive in the detection of STM and provides ample information for clinical tumour staging. PET is more sensitive compared to CT in detecting lesions in muscle, before the density and morphology of the soft tissues are altered, providing a clear view within the soft tissue. Due to the limitations in resolution, PET is less sensitive compared to CT in detecting lesions in the subcutaneous tissues. The aim of this study was to improve our knowledge of 18F-FDG PET/CT findings in the diagnosis of STM and determine its value in the staging of malignant tumours.

Dosimetric evaluation of volumetric-modulated arc therapy (RapidArc) for primary leiomyosarcoma in the spine.

This study aims to investigate the suitability of volumetric-modulated arc therapy (VMAT) with RapidArc for primary leiomyosarcoma (LMS) in the spine, and present a new method to improve the target coverage and organs at risk (OAR) sparing. Five patients with LMS were retrospectively reviewed. The intensity-modulated radiotherapy (IMRT) with five coplanar beams (5b-IMRT) or seven coplanar beams (7b-IMRT), and VMAT using four quasi-quarter coplanar arcs (4q-VMAT) or two full coplanar arcs (2f-VMAT) were generated. Planning target volume (PTV) dose coverage, OAR dose sparing, conformity index (CI), and homogeneity index (HI) were evaluated. A hollow-cylinder model (HCM) was also used for feasible optimal beam arrangements. The mean doses to PTV were 95.2% ± 1.0%, 93.0% ± 1.0%, 97.9% ± 1.0% and 96.2% ± 1.5% for 4q-VMAT, 2f-VMAT, 5b-IMRT and 7b-IMRT respectively, while the mean maximum doses to spinal cord (SC) were 43.7 ± 0.9 Gy, 42.0 ± 0.8 Gy, 41.4 ± 1.2 Gy and 40.6 ± 1.4 Gy. Compared to 5b-IMRT, the mean doses delivered to kidneys decreased by about 35.1% (8.5 Gy), 2.5% (0.6 Gy) and 35.5% (8.6 Gy) for 4q-VMAT, 2f-VMAT, and 7b-IMRT, respectively. The CI proposed by Baltas et al. was twice as good with IMRT than with 4q-VMAT, and the numbers of monitor units were increased five- and threefold with 7b-IMRT and with 5b-IMRT compared to VMAT. The unexpected results we presented here show that VMAT technique can't achieve highly conformal treatment plans while maintaining SC sparing for LMS in the spine. An approach is proposed based on a hollow-cylinder model, but it is difficult to apply to clinical practice. In this case, VMAT is not superior to IMRT except for significant reduction in delivery time.

[Effects of recombinant human interleukin 11 on hematological malignancy after allogeneic hematopoietic cell transplantation].

OBJECTIVE: To investigate the effects of recombinant human interleukin 11 (rhIL-11) on hematological malignancy after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 48 patients with hematological malignancy from January 2006 to June 2010 were alternately enrolled into a prospective randomized study. And they were assigned into the control and rhIL-11 injection groups. Later the investigators compared two groups with regards to hematopoietic reconstitution, graft versus host disease (GVHD) classification, clinical recurrence rate and disease-free survival. RESULTS: With the therapy of rhIL-11, the absolute neutrophil counts recovering to 0.5 × 10(9)/L and platelet recovering to 20 × 10(9)/L were (15.1 ± 1.6) and (18.2 ± 3.3) days respectively. And they were significantly lower than those in control group [(16.1 ± 1.6) vs (22.4 ± 5.5) days, P = 0.032, 0.003]. The incidence of acute GVHD was surprisingly low in the study group (26.1% vs 50.0%, P = 0.048). There was no significant difference in chronic GVHD (36.8% vs 38.9%, P = 0.899) or relapse rate (5.1% vs 7.7%, P = 0.662) between two groups during a median follow-up period of 11.7 months. A trend of improved 3-year-disease-free survival was observed in the study group (65.4% vs 50.9%, P = 0.637). CONCLUSION: The application of rhIL-11 after allo-HSCT may accelerate both neutrophil and platelet engraftment and lower the occurrence of acute GVHD.