Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies.

The greater efficacy of DNA-damaging drugs for pancreatic adenocarcinoma (PDAC) relies on targeting cancer-specific vulnerabilities while sparing normal organs and tissues due to their inherent toxicities. We tested LP-184, a novel acylfulvene analog, for its activity in preclinical models of PDAC carrying mutations in the DNA damage repair (DDR) pathways. Cytotoxicity of LP-184 is solely dependent on prostaglandin reductase 1 (PTGR1), so that PTGR1 expression robustly correlates with LP-184 cytotoxicity in vitro and in vivo. Low-passage patient-derived PDAC xenografts with DDR deficiencies treated ex vivo are more sensitive to LP-184 compared with DDR-proficient tumors. Additional in vivo testing of PDAC xenografts for their sensitivity to LP-184 demonstrates marked tumor growth inhibition in models harboring pathogenic mutations in ATR, BRCA1, and BRCA2. Depletion of PTGR1, however, completely abrogates the antitumor effect of LP-184. Testing combinatorial strategies for LP-184 aimed at deregulation of nucleotide excision repair proteins ERCC3 and ERCC4 established synergy. Our results provide valuable biomarkers for clinical testing of LP-184 in a large subset of genetically defined characterized refractory carcinomas. High PTGR1 expression and deleterious DDR mutations are present in approximately one third of PDAC making these patients ideal candidates for clinical trials of LP-184.

A novel sensor-embedded holding device for monitoring upper extremity functions.

There are several causes that can lead to functional weakness in the hands or upper extremities (UE), such as stroke, trauma, or aging. Therefore, evaluation and monitoring of UE rehabilitation have become essential. However, most traditional evaluation tools (TETs) and assessments require clinicians to assist or are limited to specific clinical settings. Several novel assessments might apply to wearable devices, yet those devices will still need clinicians or caretakers to help with further tests. Thus, a novel UE assessment device that is user-friendly and requires minimal assistance would be needed. The cylindrical grasp is one of the common UE movements performed in daily life. Therefore, a cylindrical sensor-embedded holding device (SEHD) for training and monitoring was developed for a usability test within this research. The SEHD has 14 force sensors with an array designed to fit holding positions and a six-axis inertial measurement unit (IMU) to monitor grip strength, hand dexterity, acceleration, and angular velocity. Six young adults, six healthy elderly participants, and three stroke survivors had participated in this study to see if the SEHD could be used as a reference to TETs. During result analyses, where the correlation coefficient analyses were applied, forearm rotation smoothness and the Purdue Pegboard Test (PPT) showed a moderate negative correlation [r (16) = -0.724, p < 0.01], and the finger independence showed a moderate negative correlation with the PPT [r (10) = -0.615, p < 0.05]. There was also a highly positive correlation between the maximum pressing task and Jamar dynamometer in maximum grip strength [r (16) = 0.821, p < 0.01]. These outcomes suggest that the SEHD with simple movements could be applied as a reference for users to monitor their UE ability.

Practical Clinical Implementation of the Special Physics Consultation Process in the Re-irradiation Environment.

PURPOSE: The purpose of this work is to present a practical, structured process allowing for consistent, safe radiation therapy delivery in the re-treatment environment. METHODS AND MATERIALS: A process for reirradiation is described with documentation in the form of a special physics consultation. Data acquisition associated with previous treatment is described from highest to lowest quality. Methods are presented for conversion to equieffective dose, as well as our departmental assumptions for tissue repair. The generation of organ-at-risk available physical dose for use in treatment planning is discussed. Results using our methods are compared with published values after conversion to biologically effective dose. Utilization of pulsed-low-dose-rate delivery is described, and data for reirradiation using these methods over the previous 5 years are presented. RESULTS: Between 2015 and 2019, the number of patients in our department requiring equieffective dose calculation has doubled. We have developed guidelines for estimation of sublethal damage repair as a function of time between treatment courses ranging from 0% for <6 months to 50% for >1 year. These guidelines were developed based on available spinal cord data because we found that 84% of organs at risk involved nerve-like tissues. The average percent repair used increased from 32% to 37% over this time period. When comparing the results obtained using our methods with published values, 99% of patients had a cumulative biologically effective dose below the limits established for acceptable myelopathy rates. Pulsed-low-dose-rate use over this period tripled with an average prescription dose of 49 Gy. CONCLUSIONS: The methods described result in safe, effective treatment in the reirradiation setting. Further correlation with patient outcomes and side effects is warranted.

Highly efficient phototheranostics of macrophage-engulfed Gram-positive bacteria using a NIR luminogen with aggregation-induced emission characteristics.

Although phagocytosis serves as the front line to attack invading pathogens, its low bacterial encounter and killing rates leads to an ineffective bactericidal output. In view of this, developing multifunctional theranostic probe to effectively discriminate and ablate intracellular bacteria is highly desirable. However, the shielding effect of the host macrophages put the detection and elimination of macrophage-engulfed bacteria into a challenging task. Herein, we utilize a luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, as a simple and effective probe for simultaneous tracing and photodynamic killing of intracellular Gram-positive bacteria. With the help of the AIE property, excellent water solubility, near-infrared (NIR) emission and strong reactive oxygen species (ROS) generating ability, TTVP performed ideally to be a targeting agent to intracellular Gram-positive bacteria with high signal contrast, as well as to be a photosensitizer to effectively ablate intracellular bacteria without attacking host macrophages. This work thus provides insights for the next generation antibiosis theranostic application for potential clinical trials.

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

LINC01939 inhibits the metastasis of gastric cancer by acting as a molecular sponge of miR-17-5p to regulate EGR2 expression.

Accumulating evidence have suggested that long noncoding RNAs (lncRNAs) are known to regulate diverse tumorigenic processes. Recently, a novel lncRNA LINC01939 was underexpressed and emerged as a tumor suppressive lncRNA in gastric cancer (GC). In this study, we aimed to investigate the biological function and molecular mechanism of LINC01939 in GC. We found that LINC01939 expression was significantly downregulated in GC tissues and cell lines. Low expression of LINC01939 was correlated with tumor metastasis and shorter survival in GC patients. Functionally, LINC01939 overexpression remarkably inhibited the invasion and migration of GC cells in vitro and in vivo. Mechanistically, LINC01939 regulated the expression of early growth response 2 (EGR2) protein by competitively binding to miR-17-5p. Upregulation of miR-17-5p reversed GC metastasis and EMT process caused by LINC01939 by rescue analysis. Taken together, these results suggested that LINC01939 repressed GC invasion and migration by functioning as a ceRNA for miR-17-5p to regulate EGR2 expression. Our findings provided a novel prognostic marker and therapeutic target for GC patients.

CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K/AKT signaling.

Calcium activated Chloride Channel A4 (CLCA4), as a tumor suppressor, was reported to contribute to the progression of several malignant tumors, yet little is known about the significance of CLCA4 in invasion and prognosis of hepatocellular carcinoma (HCC). CLCA4 expression was negatively correlated with tumor size, vascular invasion and TNM stage. Kaplan-Meier analysis showed that CLCA4 was an independent predictor for overall survival (OS) and time to recurrence (TTR). In addition, CLCA4 status could act as prognostic predictor in different risk of subgroups. Moreover, combination of CLCA4 and serum AFP could be a potential predictor for survival in HCC patients. Furthermore, CLCA4 may inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling. Knockdown of CLCA4 significantly increased the migration and invasion of HCC cells and changed the expression pattern of EMT markers and PI3K/AKT phosphorylation. An opposite expression pattern of EMT markers and PI3K/AKT phosphorylation was observed in CLCA4-transfected cells. Additionally, immunohistochemistry and RT-PCR results further confirmed this correlation. Taken together, CLCA4 contributes to migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favourable prognosis of HCC. CLCA4/AFP expression may help to distinguish different risks of HCC patients after hepatectomy.

Comparison of 3D and 2D gamma passing rate criteria for detection sensitivity to IMRT delivery errors.

This study compared three-dimensional (3D) and two-dimensional (2D) percentage gamma passing rates (%GPs) for detection sensitivity to IMRT delivery errors and investigated the correlation between two kinds of %GP. Eleven prostate IMRT cases were selected, and errors in multileaf collimator (MLC) bank sag, MLC leaf traveling, and machine output were simulated by recalculating the dose distributions in patients. 2D doses were extracted from the 3D doses at the isocenter position. The 3D and 2D %GPs with different gamma criteria were then obtained by comparing the recalculated and original doses in specific regions of interest (ROI), such as the whole body, the planning target volume (PTV), the bladder, and the rectum. The sensitivities to simulated errors of the two types of %GP were compared, and the correlation between the 2D and 3D %GPs for different ROIs were analyzed. For the whole-body evaluation, both the 2D and 3D %GPs with the 3%/3 mm criterion were above 90% for all tested MLC errors and for MU deviations up to 4%, and the 3D %GP was higher than the 2D %GP. In organ-specific evaluations, the PTV-specific 2D and 3D %GP gradients were -4.70% and -5.14% per millimeter of the MLC traveling error, and -17.79% and -20.50% per percentage of MU error, respectively. However, a stricter criterion (2%/1 mm) was needed to detect the tested MLC sag error. The Pearson correlation analysis showed a significant strong correlation (r > 0.8 and P < 0.001) between the 2D and 3D %GPs in the whole body and PTV-specific gamma evaluations. The whole-body %GP with the 3%/3 mm criterion was inadequate to detect the tested MLC and MU errors, and a stricter criterion may be needed. The PTV-specific gamma evaluation helped to improve the sensitivity of the error detection, especially using the 3D GP%.

Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS.

Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer.

HOXC6 predicts invasion and poor survival in hepatocellular carcinoma by driving epithelial-mesenchymal transition.

Aberrant expression of HOXC6 has been reported in several malignant tumors, yet little is known about the value of HOXC6 in invasion and prognosis of hepatocellular carcinoma (HCC). HOXC6 expression was positively correlated with high AFP level, liver cirrhosis, larger tumor, vascular invasion and BCLC stage. Kaplan-Meier analysis revealed that HOXC6 was an independent predictor for overall survival (OS) and time to recurrence (TTR). In addition, HOXC6 status could act as prognostic predictor in different risk subgroups. Moreover, HOXC6 maintained its prognostic value in different ability of invasiveness. Furthermore, combination of HOXC6 and serum AFP could be a potential predictor for survival in HCC patients. Additionally, further study showed that HOXC6 may promote invasion of HCC by driving epithelial-mesenchymal transition (EMT). Knockdown of HOXC6 significantly decreased the migration and invasion of HCC cells and changed the expression pattern of EMT markers. An opposite expression pattern of EMT markers was observed in HOXC6-transfected cells. In addition, immunohistochemistry and RT-PCR results further confirmed this correlation. In conclusion, HOXC6 contributes to invasion by inducing EMT pathway and predicts poor prognosis of HCC. HOXC6/AFP expression may help to distinguish the different risks of HCC patients after hepatectomy.

A treatment planning comparison between a novel rotating gamma system and robotic linear accelerator based intracranial stereotactic radiosurgery/radiotherapy.

To compare the dosimetric parameters of a novel rotating gamma ray system (RGS) with well-established CyberKnife system (CK) for treating malignant brain lesions. RGS has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. We compared several dosimetric parameters in 10 patients undergoing brain stereotactic radiosurgery including plan normalization, number of beams and nodes for CK and shots for RGS, collimators used, estimated treatment time, D 2 cm and conformity index (CI) among two modalities. The median plan normalization for RGS was 56.7% versus 68.5% (p = 0.002) for CK plans. The median number of shots from RGS was 7.5 whereas the median number of beams and nodes for CK was 79.5 and 46. The median collimator's diameter used was 3.5 mm for RGS as compared to 5 mm for CK (p = 0.26). Mean D 2 cm was 5.57 Gy for CyberKnife whereas it was 3.11 Gy for RGS (p = 0.99). For RGS plans, the median CI was 1.4 compared to 1.3 for the CK treatment plans (p = 0.98). The average minimum and maximum doses to optic chiasm were 21 and 93 cGy for RGS as compared to 32 and 209 cGy for CK whereas these were 0.5 and 364 cGy by RGS and 18 and 399 cGy by CK to brainstem. The mean V12 Gy for brain predicting for radionecrosis with RGS was 3.75 cm3 as compared to 4.09 cm3 with the CK (p = 0.41). The dosimetric parameters of a novel RGS with a ring type gantry are comparable with CyberKnife, allowing its use for intracranial lesions and is worth exploring in a clinical setting.

A textured insole improves gait symmetry in individuals with stroke.

PURPOSE: Gait asymmetry is a common consequence of stroke and improving gait symmetry is an important goal of rehabilitation. We investigated the effect of a single textured insole in improving gait symmetry in individuals with stroke. METHOD: Seventeen individuals with stroke who had asymmetrical gait were recruited and required to walk with a textured insole positioned in the shoe on the unaffected side or without the insole. Gait parameters were evaluated using the instrumented walkway. Gait velocity, cadence, and symmetry indices for the spatial and temporal parameters of gait and center of pressure displacements were obtained. RESULTS: When walking with a textured insole, symmetry indexes for stance, single support phases of gait, as well as center of pressure displacements improved significantly. While using a textured insole, the duration of the stance phase and a single support phase decreased on the unaffected side and increased on the affected side significantly. Gait velocity and cadence were not affected by the use of the insole. CONCLUSIONS: Individuals with stroke walking with a textured insole placed in the shoe on the unaffected side improved the symmetry of their gait. The outcome provides a foundation for future investigations of the efficacy of using a single textured insole in gait rehabilitation of individuals with unilateral impairment. Implications for Rehabilitation A single textured insole positioned in the shoe on the unaffected side improved gait symmetry in individuals with stroke. Gait velocity and cadence were not affected by the use of the insole.

Redox-dependent modulation of metformin contributes to enhanced sensitivity of esophageal squamous cell carcinoma to cisplatin.

Glutathione is the major intracellular anti-oxidant against reactive oxygen species and serves as a detoxification essential. The anti-diabetic drug metformin has been showed to exert anti-tumor activity via modulation of redox homeostasis. In this study, we provided evidence that metformin inhibits proliferation and induces apoptosis of esophageal squamous cancer cells. Importantly, we found that metformin acts as pro-oxidant via depletion of intracellular glutathione. Co-treatment with metformin reversed the elevated intracellular glutathione induced by cisplatin and therefore enhanced the sensitivity to cisplatin in vitro and in vivo. Taken together, our data indicate that combination of metformin with cisplatin may represent a novel therapeutic strategy for esophageal squamous cell carcinoma treatment.

GPX2 overexpression indicates poor prognosis in patients with hepatocellular carcinoma.

Glutathione peroxidase 2 has important role of tumor progression in lots of carcinomas, yet little is known about the prognosis of glutathione peroxidase 2 in hepatocellular carcinoma. Glutathione peroxidase 2 expression was assessed by immunohistochemistry in hepatocellular carcinoma tissues. The association between glutathione peroxidase 2 expression with clinicopathological/prognostic value was examined. Glutathione peroxidase 2 overexpression was correlated with alpha-fetoprotein level, larger tumor, BCLC stage, and tumor recurrence. Kaplan-Meier analysis showed that glutathione peroxidase 2 was an independent predictor for overall survival and time to recurrence. glutathione peroxidase 2 overexpression was correlated with poor prognosis in patient subgroups stratified by tumor size, differentiation, tumor-node-metastasis, and BCLC stage. Moreover, stratified analysis showed that tumor-node-metastasis stage-I patients with high glutathione peroxidase 2 expression had poor prognosis than those with low glutathione peroxidase 2 expression. Additionally, combination of glutathione peroxidase 2 and serum alpha-fetoprotein was correlated with prognosis in hepatocellular carcinoma. In conclusion, glutathione peroxidase 2 overexpression contributes to poor prognosis of hepatocellular carcinoma patients and helps to identify the high-risk hepatocellular carcinoma patients.

Unilateral Discomfort Increases the Use of Contralateral Side during Sit-to-Stand Transfer.

Individuals with unilateral impairment perform symmetrical movements asymmetrically. Restoring symmetry of movements is an important goal of rehabilitation. The aim of the study was to evaluate the effect of using discomfort-inducing devices on movement symmetry. Fifteen healthy individuals performed the sit-to-stand (STS) maneuver using devices inducing unilateral discomfort under the left sole and left thigh or right sole and right thigh and without them. 3D body kinematics, ground reaction forces, electrical activity of muscles, and the level of perceived discomfort were recorded. The center of mass (COM), center of pressure (COP), and trunk displacements as well as the magnitude and latency of muscle activity of lower limb muscles were calculated during STS and compared to quantify the movement asymmetry. Discomfort on the left and right side of the body (thigh and feet) induced statistically significant displacement of the trunk towards the opposite side. There was statistically significant asymmetry in the activity of the left and right Tibialis Anterior, Medial Gastrocnemius, and Biceps Femoris muscles when discomfort was induced underneath the left side of the body (thigh and feet). The technique was effective in causing asymmetry and promoted the use of the contralateral side. The outcome provides a foundation for future investigations of the role of discomfort-inducing devices in improving symmetry of the STS in individuals with unilateral impairment.

Upregulation of the long non-coding RNA PVT1 promotes esophageal squamous cell carcinoma progression by acting as a molecular sponge of miR-203 and LASP1.

Long non-coding RNAs are a group of non-coding RNAs longer than 200 nucleotides and possess diverse functions and exhibit exquisite cell-specific and developmental dynamic expression patterns. The role of the long non-coding RNA PVT1 in esophageal squamous cell carcinoma remains unsolved. Here, we showed that PVT1 expression is significantly up-regulated in ESCC tumor samples compared with their normal counterparts. Knockdown of PVT1 suppressed tumor growth in vitro and in vivo. Further studies revealed that silence of PVT1 lead to up-regulation of miR-203, and vice versa. Moreover, LASP1 was found to be downregulated after knockdown of PVT1 and overexpression of LASP1 attenuated the tumor-suppressive roles of PVT1 knockdown. Our results suggest that PVT1 promote ESCC progression via functioning as a molecular sponge for miR-203 and LASP1 and provide the first evidence of dysregulated PVT1/miR-203/LASP1 axis in ESCC.

Long-Term Patient-Reported Outcomes From a Phase 3 Randomized Prospective Trial of Conventional Versus Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: To assess the long-term quality of life (QoL) outcomes from a phase 3 trial comparing 2 modes of intensity modulated radiation therapy (IMRT): conventional IMRT (CIMRT) versus hypofractionated IMRT (HIMRT) in patients with localized prostate cancer. METHODS AND MATERIALS: Between 2002 and 2006, 303 men with low-risk to high-risk prostate cancer were randomized to 76 Gy in 38 fractions (CIMRT) versus 70.2 Gy in 26 fractions (HIMRT). QoL was compared by use of the Expanded Prostate Cancer Index Composite (EPIC), the International Prostate Symptom Score (IPSS), and EuroQoL (EQ5D) questionnaires. The primary outcome of the QoL analysis was a minimum clinically important difference defined as a 0.5 standard deviation change from baseline for each respective QoL parameter. Treatment effects were evaluated with the use of logistic mixed effects regression models. RESULTS: A total of 286, 299, and 218 patients had baseline EPIC, IPSS, or EQ5D data available and were included in the analysis. Overall, there was no statistically significant difference between the 2 treatment arms in terms of EPIC, IPSS, or EQ5D scores over time, although there was a trend toward lower EPIC urinary incontinence scores in the HIMRT arm. More patients in the HIMRT arm had a lower EPIC urinary incontinence score relative to baseline versus patients in the CIMRT arm with long-term follow-up. On multivariable analysis, there was no association between radiation fractionation scheme and any QoL parameter. When other clinical factors were examined, lymph node radiation was associated with worse EPIC hormonal scores versus patients receiving no lymph node radiation. In general, QoL outcomes were generally stable over time, with the exception of EPIC hormonal and EQ5D scores. CONCLUSIONS: In this randomized prospective study, there were stable QoL changes in patients receiving HIMRT or CIMRT. Our results add to the growing body of literature suggesting that HIMRT may be an acceptable treatment modality in clinically localized prostate cancer.

LncRNA ANRIL is up-regulated in nasopharyngeal carcinoma and promotes the cancer progression via increasing proliferation, reprograming cell glucose metabolism and inducing side-population stem-like cancer cells.

Long noncoding RNAs play a vital role in diverse biological processes such as embryonic development, cell growth, and tumorigenesis. In this study, we report that LncRNA ANRIL, which encodes a 3834-nt RNA that contains 19 exons at the antisense orientation of the INK4B-ARF-INK4A gene cluster, generally up-regulated in nasopharyngeal carcinoma [1]. In a cohort of 88 NPC patients, ANRIL was highly expressed in advanced-stage cancer. Multivariate analyses revealed that ANRIL expression could serve as an independent predictor of overall survival (P = 0.027) and disease-free survival (P = 0.033). Further investigation showed that knockdown of ANRIL significantly repressed NPC cell proliferation and transformation. We also found that ANRIL could induce the percentage of side population cells (SP cells) in NPC. To meet the urgent needs of energy provision, ANRIL can also reprogram glucose metabolism via increasing glucose uptake for glycolysis, which was regulated by the mTOR signal pathway to affect the expression of essential genes in glycolysis. We concluded that ANRIL could promote NPC progression via increasing cell proliferation, reprograming cell glucose metabolism and inducing side-population stem-like cancer cells. Our results also suggested that ANRIL may serve as a novel diagnostic or prognostic biomarker and a candidate target for new therapies in NPC.

Immediate and short-term effects of wearing a single textured insole on symmetry of stance and gait in healthy adults.

Asymmetry of standing balance and gait are common in individuals with neurological or musculoskeletal disorders and achieving symmetrical stance and gait is an important goal of rehabilitation. The aim of the study was to investigate if asymmetry of stance and gait observed immediately after the start of using a single textured insole remains during longer use of the insole. Ten young healthy adults walked in two different conditions: with a textured insole positioned in the left shoe or without the insole. Weight bearing, gait, and perceived level of discomfort were evaluated before using a textured insole, immediately after being provided with the insole, and after walking for 10min with the insole. The center of pressure (COP) trajectory was calculated for the right and left foot in the insole and no-insole conditions. Asymmetry of stance and gait was present immediately after the start of using a textured insole (p<0.05) but was not evident after 10min of wearing the insole. The COP trajectory of the right foot after being provided with the left insole was significantly greater compared with walking with no insole (p<0.05). Gait velocity, cadence, and the COP trajectory of the left foot were not affected by the use of the insole. The outcome of the study provides a background for the investigation of the effect of using a textural insole in gait rehabilitation.