A small footprint couch-top support device for image-guided radiotherapy of heavy patients.

PURPOSE: Patients with body weights close to or above 400 lbs present unique challenges in radiation therapy since the weight limit of most treatment couches decreases as the couch-top extends toward the treatment gantry. The purpose of this work was to develop a small footprint couch-top support platform to safely perform image-guided radiotherapy (IGRT) for extremely heavy patients. METHODS: One way to protect the couch-top from damage and prevent a catastrophic breakdown is to provide additional support as the couch extends toward the treatment gantry. To allow a maximal range of gantry movement, a small-footprint adjustable jack stand, placed underneath the couch-top, was chosen and modified from a commercial jack stand (with 1100 lbs capacity). The couch could be easily extended longitudinally and laterally with a modified 8-ball-transfer plate mounted at the top. The operation of a couch-top support platform was used for two heavy patients after phantom testing. kV and MV imaging options and ranges were quantified. RESULTS: The custom-constructed couch-top support platform was found to provide stable support with smooth couch shifts. The small footprint allowed gantry rotation from 133° to 227°, which would allow both fixed beam radiotherapy and partial-arc volumetric modulated arc therapy (VMAT). For IGRT, orthogonal 2D kV-kV image pairs with source angles of 40o and 130o were acquired and tested successfully. With the support platform, two clinical cases with patient weights greater than 415 lbs were successfully treated with image-guided partial arc VMAT radiotherapy. The study demonstrated the safety and efficiency of using this new couch-top support platform to prevent couch failure from treating heavy patients. CONCLUSIONS: A new couch-top support platform has been designed, assembled, and tested for IGRT. The new support platform is easy to use, cost-effective, and allows extremely heavy patients to be treated safely and robustly with IGRT and VMAT.

Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Med Sci Monit 2018; 24: 6093-6101. 10.12659/MSM.909745.

Establishing the prognostic value of platelet-to-lymphocyte ratio in cervical cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to conduct a meta-analysis to establish the prognostic value of platelet-to-lymphocyte ratio in cervical cancer. METHODS: We conducted a search in Medline and Embase datasets for articles published until May 1, 2018 to perform a meta-analysis to establish the prognostic value of platelet-to-lymphocyte ratio in cervical cancer. The primary survival outcomes were overall survival and progression-free survival. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were combined to calculate overall effects. Cochran's Q test and Higgins' I2 statistics were employed to estimate the heterogeneity. In addition, the subgroup analysis, sensitivity analysis, and meta-regression were performed to identify the source of heterogeneity. Egger's linear regression test and Begg's funnel plot and the trim and fill methods were employed to evaluate the publication bias. RESULTS: A total of 2616 patients from eight studies were enrolled in the meta-analysis. Significant association was observed between elevated platelet-to-lymphocyte ratio and a worse overall survival, with a combined HR of 1.49 (95% CI 1.24 to 1.79, I2=32.8%). Elevated platelet-to-lymphocyte ratio was significantly associated with a worse progression-free survival, with a combined HR of 1.65 (95% CI 1.17 to 2.33, I2 = 49.4%). Subsequently, sensitivity analysis, subgroup analysis, and meta-regression model containing six predominant factors were applied to trace the origin of heterogeneity. However, no significant factors or studies were explored as the potential source of heterogeneity. CONCLUSION: Elevated pre-treatment platelet-to-lymphocyte ratio may be an adverse prognostic factor for overall survival and progression-free survival in patients with cervical cancer. Further investigations are warranted to determine the exact mechanism by which platelet-to-lymphocyte ratio impacts survival outcomes in cervical cancer.

Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.

BACKGROUND Ovarian cancer is considered one of the lethal cancers responsible for high mortality and morbidity across the world. The prognosis and the survival rate of ovarian cancer is far from decent. Cysteine-rich 61 (Cyr61) also known as CCN1, is a member of CCN-family of growth factors, reported to be significantly overexpressed in several malignancies which include, but are not limited to, ovarian cancer. Recent studies have revealed that women with type 2 diabetes mellitus have an elevated risk of ovarian cancer. Hence, administration of an antidiabetic drug with anticancer effects such as metformin may act as an effective therapeutic regime against ovarian cancer. MATERIAL AND METHODS Cell viability and apoptosis were examined by MTT and Annexin V/PI double staining respectively. Cell migration was determined by Boyden Chamber assay. Transient knockdown of Cyr61 in ovarian cancer cells was achieved by transecting the cells with siRNA for Cyr61using Lipofectamine 2000. RESULTS Our results indicated that treatment of ovarian cancer cells with metformin caused significant downregulation of Cyr61 protein expression levels ultimately favoring apoptosis. Transient knockdown of Cyr61 resulted in the inhibition of cell proliferation and migration. This was also associated with the concomitant downregulation of pAkt and pmTOR confirming the role of Cyr61 as an upstream modulator of Akt signaling. Conversely the extracellular supplementation of recombinant Cyr61 attenuates the cytotoxic properties of metformin in ovarian cancer cells. CONCLUSIONS Taken together, we concluded that metformin exhibits anticancer effects and Cyr61 acts as a direct target for metformin in ovarian cancer cells.

Effects of Septum Resection for Secondary Infertility on Subsequent Reproductive Outcomes of in vitro Fertilization-Intracytoplasmic Sperm Injection.

OBJECTIVE: To assess the effect of uterine septum resection on reproductive outcomes of in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) in patients with secondary infertility complicated with uterine septum. METHODS: A retrospective cohort study included 269 patients. Surgical group included 169 patients with secondary infertility complicated with uterine septum, who underwent 252 embryo-transfer (ET) cycles following septum resection. Control group consisted of 100 patients with secondary infertility and uterine septum, who underwent 178 ET cycles. Cumulative pregnancy rate and cumulative live birth rate after one complete assisted reproductive technology (ART) cycle were the primary outcomes. RESULTS: The results showed that the cumulative pregnancy rate was higher in the surgery group, and statistically significant difference was observed in the cumulative pregnancy rate between the two groups (71.0 vs. 59%, P = 0.044). In fresh ET cycle, no statistically significant difference between the two groups was evident (54.9 vs. 40.6%, P = 0.061). Statistical analysis of other results of the fresh ET cycle did not differ significantly between the two groups. In terms of frozen embryo transfer (FET) cycle outcomes, the clinical pregnancy rate and delivery rate in surgery group were 52.7 and 38.2%, respectively, which were significantly higher than those in the control group (38.2 and 22.5%, respectively) (P = 0.028 and P = 0.011). CONCLUSION: The reproductive outcomes of IVF/ICSI after septum resection in patients with secondary infertility were better than that in the untreated group, suggesting that uterine septum resection can be performed in patients with uterine septum combined with infertility to improve their reproductive outcomes.

MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8.

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

Effect of hysteroscopic septum resection on subsequent in vitro fertilization-intracytoplasmic sperm injection outcomes in cases of primary infertility.

OBJECTIVE: Women with septate uteri are at risk for subfertility, recurrent miscarriage, and preterm birth. It is not clear if hysteroscopic septum resection is beneficial to subsequent in vitro fertilization-intracytoplasmic sperm injection o (IVF/ICSI) outcomes in women with primary infertility. STUDY DESIGN: We analyzed all 278 women with uterine septum and primary infertility between January 2011 and January 2019. In this retrospective cohort study, the patients were divided into a surgery group and an expectant (non-surgery) group. RESULTS: Among them, 87 had a complete and 191 a partial septate uterus. The IVF-ET characteristics of the two groups showed no significant differences in the patients' age, body mass index, or basal follicle-stimulating hormone, luteinizing hormone, and estradiol levels (P>0.05). The miscarriage rate in those who underwent hysteroscopic septum resection, however, was significantly reduced (5.1% vs. 12.9%, P = 0.035). In contrast, the live birth rate between the two groups revealed no significant difference (51.4% vs. 43.6%, P = 0.1771), nor did the obstetric and neonatal outcomes (P>0.05). CONCLUSIONS: Hysteroscopic septum resection can be recommended prior to IVF/ICSI.

MicroRNA-103 regulates the progression in endometrial carcinoma through ZO-1.

Endometrial carcinoma (EC) is one of the most common gynecological cancers in many developing countries. Although tremendous advances have been made in the diagnosis and treatment of EC, there is still no adequate biomarker currently available for predicting the prognosis of this cancer. In this study, we found that miR-103 expression was significantly upregulated in EC tissues than their paired non-carcinoma tissues. Overexpression of miR-103 significantly promoted EC cell proliferation, while downregulation of miR-103 significantly suppressed EC cell proliferation. In addition, ZO-1 expression was significantly downregulated in the EC tissues than their paired non-carcinoma tissues. We also found an inverse correlation between ZO-1 and miR-103. Moreover, ZO-1 was validated as the direct target of miR-103. The downregulation of ZO-1 significantly enhanced EC cell proliferation. In conclusion, miR-103 could regulate EC cell proliferation through directly targeting ZO-1. Our results provide a potential development of microRNA-based targeted approaches for the treatment of EC.

Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits.

BACKGROUND: Recent studies have revealed that pretreatment with statin is effective in preventing arrhythmia, but its electrophysiological mechanism is unclear. This study was conducted to investigate the cardioprotective effects of simvastatin on reversing electrical remodeling in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the ionic mechanism responsible for the anti-arrhythmic effect of statin. METHODS: Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (Statin) and sham-operated control group (CON). Anesthetized rabbits were subjected to 30-minute ischemia by ligation of the left anterior descending coronary artery and a 60-minute reperfusion after a 3-day administration of oral simvastatin of 5 mg x kg(-1) x d(-1) in the Statin group or a placebo in the I-R group. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in the I-R and Statin group and the same anatomical region in the CON animals. The whole cell patch-clamp technique was used to record membrane ionic currents, including sodium current (I(Na)), L-type calcium current (I(Ca-L)) and transient outward potassium current (I(to)). Simultaneously, the level of serum cholesterol was examined. RESULTS: There was no significant difference in the serum cholesterol concentration among the three groups. The peak I(Na) current density (at -30 mV) was significantly decreased in I-R ((-22.46+/-5.32) pA/pF, n=12) compared with CON ((-42.78+/-5.48) pA/pF, n=16, P<0.01) and Statin ((-40.66+/-5.89) pA/pF, n=15, P<0.01), while the peak I(Na) current density in the Statin group was not different from CON (P>0.05). The peak I(Ca-L) current density (at 0 mV) was significantly increased in I-R ((-4.34+/-0.92) pA/pF, n=15) compared with CON ((-3.13+/-1.22) pA/pF, n=13, P<0.05) and Statin ((-3.46+/-0.85) pA/pF, n=16, P<0.05), while the Peak I(Ca-L) current density in Statin was not different from CON (P>0.05). The I(to) current density (at +60 mV) was significantly decreased in I-R ((9.49+/-1.91) pA/pF, n=11) compared with CON ((17.41+/-3.13) pA/pF, n=15, P<0.01) and Statin ((14.54+/-2.41) pA/pF, n=11, P<0.01), although there was a slight reduction in the Statin group compared with CON (P<0.05). CONCLUSIONS: It is implied that ischemia-reperfusion induces significant down-regulation of I(Na) and I(to) and up-regulation of I(Ca-L), which may underlie the altered electrical activity and long abnormal transmembrane action potential duration of the surviving ventricular myocytes, thus contributing to ventricular arrhythmias during acute ischemia-reperfusion period. Pretreatment with simvastatin could attenuate these changes and reverse this electrical remodeling without lowering the serum cholesterol level, contributing to the ionic mechanism of statin in treatment of arrhythmia independent of a decrease in cholesterol.

MicroRNA-183 correlates cancer prognosis, regulates cancer proliferation and bufalin sensitivity in epithelial ovarian caner.

Background we intended to explore the functional implication of microRNA-183 (miR-183) in predicting clinical prognosis and regulating cancer proliferation and bufalin sensitivity in epithelial ovarian cancer (EOC). Methods In 75 EOC patients, miR-183 expression was examined, by quantitative RT-PCR (qRT-PCR), between paired EOC tumors and adjacent normal tissues, and between tumor samples from patients at early clinical stages and those at advanced clinical stages. The association of serum miR-183 and patients' clinicopathological variables were examined. The overall survival (OS) was estimated by Kaplan-Meier model. And the possibility of miR-183 as a prognostic biomarker for EOC was examined by cox proportional hazard regression model. In EOC cell lines SKOV3 and ES-2 cells, lentiviral transduction was conducted to genetically suppress miR-183. The effect of miR-183 downregulation on EOC in vitro growth, bufalin sensitivity and in vivo tumorigenicity were examined. Results MiR-183 was highly expressed in EOC tumors, as well ass in patients at advanced clinical stages. Serum miR-183 was significantly associated with major clinicopathological variables in EOC patients, such as clinical stage and lymph node metastases. High level of serum miR-183 was associated with poor OS in EOC patients, and proved to be a potential biomarker for EOC. In EOC cell lines, functional assays demonstrated that miR-183 downregulation inhibited cancer proliferation, enhanced bufalin sensitivity and reduced tumorigenicity in vivo. Conclusion MiR-183 may be a prognostic biomarker for EOC, and inhibiting miR-183 may have therapeutic effect to inhibit tumor growth in EOC.

[Evaluation of three-dimensional conformal radiotherapy based on dose distribution].

In this paper, we briefly introduce 3 methods of evaluation for a treatment plan, and mainly discuss the criteria of the plan's optimization based on dose distribution. The elaboratively-designed treatment plan is capable of having the tumor receive higher dose level while the normal tissues and organs receive minimum dose level.

Efficiency gains for spinal radiosurgery using multicriteria optimization intensity modulated radiation therapy guided volumetric modulated arc therapy planning.

PURPOSE: To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. METHODS AND MATERIALS: MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. RESULTS: The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively (P < .05). CONCLUSIONS: The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced by nominally 25% with VMAT.

Multicriteria optimization informed VMAT planning.

We developed a patient-specific volumetric-modulated arc therapy (VMAT) optimization procedure using dose-volume histogram (DVH) information from multicriteria optimization (MCO) of intensity-modulated radiotherapy (IMRT) plans. The study included 10 patients with prostate cancer undergoing standard fractionation treatment, 10 patients with prostate cancer undergoing hypofractionation treatment, and 5 patients with head/neck cancer. MCO-IMRT plans using 20 and 7 treatment fields were generated for each patient on the RayStation treatment planning system (clinical version 2.5, RaySearch Laboratories, Stockholm, Sweden). The resulting DVH of the 20-field MCO-IMRT plan for each patient was used as the reference DVH, and the extracted point values of the resulting DVH of the MCO-IMRT plan were used as objectives and constraints for VMAT optimization. Weights of objectives or constraints of VMAT optimization or both were further tuned to generate the best match with the reference DVH of the MCO-IMRT plan. The final optimal VMAT plan quality was evaluated by comparison with MCO-IMRT plans based on homogeneity index, conformity number of planning target volume, and organ at risk sparing. The influence of gantry spacing, arc number, and delivery time on VMAT plan quality for different tumor sites was also evaluated. The resulting VMAT plan quality essentially matched the 20-field MCO-IMRT plan but with a shorter delivery time and less monitor units. VMAT plan quality of head/neck cancer cases improved using dual arcs whereas prostate cases did not. VMAT plan quality was improved by fine gantry spacing of 2 for the head/neck cancer cases and the hypofractionation-treated prostate cancer cases but not for the standard fractionation-treated prostate cancer cases. MCO-informed VMAT optimization is a useful and valuable way to generate patient-specific optimal VMAT plans, though modification of the weights of objectives or constraints extracted from resulting DVH of MCO-IMRT or both is necessary.

Stereotactic, single-dose irradiation of lung tumors: a comparison of absolute dose and dose distribution between pencil beam and Monte Carlo algorithms based on actual patient CT scans.

PURPOSE: Dose calculation based on pencil beam (PB) algorithms has its shortcomings predicting dose in tissue heterogeneities. The aim of this study was to compare dose distributions of clinically applied non-intensity-modulated radiotherapy 15-MV plans for stereotactic body radiotherapy between voxel Monte Carlo (XVMC) calculation and PB calculation for lung lesions. METHODS AND MATERIALS: To validate XVMC, one treatment plan was verified in an inhomogeneous thorax phantom with EDR2 film (Eastman Kodak, Rochester, NY). Both measured and calculated (PB and XVMC) dose distributions were compared regarding profiles and isodoses. Then, 35 lung plans originally created for clinical treatment by PB calculation with the Eclipse planning system (Varian Medical Systems, Palo Alto, CA) were recalculated by XVMC (investigational implementation in PrecisePLAN [Elekta AB, Stockholm, Sweden]). Clinically relevant dose-volume parameters for target and lung tissue were compared and analyzed statistically. RESULTS: The XVMC calculation agreed well with film measurements (<1% difference in lateral profile), whereas the deviation between PB calculation and film measurements was up to +15%. On analysis of 35 clinical cases, the mean dose, minimal dose and coverage dose value for 95% volume of gross tumor volume were 1.14 ± 1.72 Gy, 1.68 ± 1.47 Gy, and 1.24 ± 1.04 Gy lower by XVMC compared with PB, respectively (prescription dose, 30 Gy). The volume covered by the 9 Gy isodose of lung was 2.73% ± 3.12% higher when calculated by XVMC compared with PB. The largest differences were observed for small lesions circumferentially encompassed by lung tissue. CONCLUSIONS: Pencil beam dose calculation overestimates dose to the tumor and underestimates lung volumes exposed to a given dose consistently for 15-MV photons. The degree of difference between XVMC and PB is tumor size and location dependent. Therefore XVMC calculation is helpful to further optimize treatment planning.