A backward cycling programme for people with Parkinson's disease: a feasibility and preliminary results study.

OBJECTIVE: To assess the feasibility of backward cycling for people with Parkinson's disease. Secondary objectives were to assess changes in gait and balance following a 6-week program. DESIGN: A single-group prospective pre-test, post-test study with 1-month follow-up. SUBJECTS/PATIENTS: Twenty-six people with Parkinson's disease (mean age: 69 (7.74) years, gender: 83% males, time since diagnosis: 6 (4.44) years). METHODS: Participants pedaled backward on a stationary bicycle for 30 minutes at moderate intensity twice a week for 6 weeks. Feasibility was assessed by acceptability, suitability, and burden. Data collected at pre- and post-intervention with 1-month follow-up included backward stepping response variables, forward/backward gait variables, Mini-Balance Evaluation Systems Test (MBT), and 6 Minute Walk Test. RESULTS: There was a high retention rate (95.8%) and adherence rate (100%) with one adverse event and minimal burden. Significant improvements were seen in step count and excursion distance during backward stepping responses, forward and backward gait velocity, forward step length, and the Mini-BESTest. CONCLUSION: Backward cycling was a feasible intervention for people with Parkinson's disease, demonstrating low burden with high retention and adherence rates, and it is a safe exercise with the potential for benefits in gait and balance variables.

Evaluating clinical reasoning in first year DPT students using a script concordance test.

BACKGROUND: A script concordance test (SCT) provides a series of clinical vignettes to assess clinical reasoning in uncertainty. Appraised throughout health education literature, SCTs are cognitive assessments of clinical reasoning, though their use in Doctor of Physical Therapy (DPT) entry-level education has not been investigated. The purpose of this study was to develop and explore the reliability and validity of a SCT for first year DPT students. METHODS: The SCT was developed and implemented over four phases. During phases one and two, DPT program faculty consulted on course content from the first-year curriculum. Thirty clinical vignettes with three follow-up questions each were constructed. The SCT was pilot tested with five clinicians in phase three to assess question clarity. During phase four, the SCT was administered to students and a reference panel via Qualtrics. First year DPT students (n = 44) and reference panel physical therapists with at least two years of experience and advanced certification (n = 15) completed the SCT. Internal consistency was analyzed using Cronbach's Alpha. Differences between student and reference panel percent-correct scores were analyzed with a t-test. Relationships between student SCT scores and academic records were explored with Spearman's Rho. RESULTS: The SCT had an internal consistency of 0.74. A significant difference in scores was found between the students [mean 58.5 (+/-5.31)] and reference panel [65.8 (+/-4.88), p < .01]. No significant correlations between student SCT scores and academic records were found. CONCLUSIONS: The developed SCT was reliable and demonstrated satisfactory internal consistency among test items. The SCT successfully differentiated between groups, with the reference panel demonstrating statistically significant higher percent-correct scores compared to students. SCTs may provide means to measure clinical reasoning in DPT students and lead to novel pedagogical approaches to enhance clinical reasoning.

Floor-to-Stand Performance Among People Following Stroke.

OBJECTIVES: Studies have examined floor-to-stand performance in varied adult populations both quantitatively and qualitatively. Despite an elevated risk of falls and inability to independently return to stand after a fall, few have examined the ability to stand from the floor in patients recovering from stroke. There were 2 objectives of the study: to identify the relationships between floor-to-stand performance using a timed supine-to-stand test (TSS) and physical performance measures of gait, balance, and balance confidence among persons in the subacute phase after stroke; and to analyze descriptive strategies used in the completion of the TSS. METHODS: A cross-sectional design was implemented. Fifty-eight adults (mean age = 59.2 [standard deviation (SD) = 13.9] years; 34 [58.6%] men) who were in the subacute phase after ischemic or hemorrhagic stroke and who could stand from the floor with no more than supervision completed the TSS and physical performance assessments. RESULTS: The median time to complete the TSS in our sample was 13.0 (interquartile range = 15.5) seconds. TSS time was significantly correlated with physical performance tests, including the Timed "Up & Go" Test (ρ = 0.70), gait speed (ρ = -0.67), Dynamic Gait Index (ρ = -0.52), and Activities-Specific Balance Confidence Scale (ρ = -0.43). Thirty-two percent of the variance in TSS time was attributed to Timed "Up & Go" Test time and the use of the quadruped position to transition to standing. Participants who used a gait device were more likely to use a chair during rise to stand. CONCLUSION: The TSS demonstrates concurrent validity with physical performance measures. IMPACT: Findings serve to improve functional mobility examination after stroke and to formulate effective treatment interventions to improve floor-to-stand performance.

A Systematic Appraisal of Conflicts of Interest and Researcher Allegiance in Clinical Studies of Dry Needling for Musculoskeletal Pain Disorders.

OBJECTIVE: The purpose of this study was to determine the frequency and methods of conflicts of interest (COI) reporting in published dry needling (DN) studies and to determine the frequency of researcher allegiance (RA). METHODS: A pragmatic systematic search was undertaken to identify DN studies that were included in systematic reviews. Information regarding COI and RA were extracted from the full text of the published DN reports, and study authors were sent a survey inquiring about the presence of RA. A secondary analysis also was undertaken based on study quality/risk of bias scores that were extracted from the corresponding systematic reviews and study funding extracted from each DN study. RESULTS: Sixteen systematic reviews were identified, containing 60 studies of DN for musculoskeletal pain disorders, 58 of which were randomized controlled trials. Of the DN studies, 53% had a COI statement. None of these studies disclosed a COI. Nineteen (32%) authors of DN studies responded to the survey. According to the RA survey, 100% of DN studies included at least 1 RA criterion. According to the data extraction, 1 RA criterion was met in 45% of the DN studies. The magnitude of RA per study was 7 times higher according to the surveys than in the published reports. CONCLUSION: These results suggest that COI and RA might be underreported in studies of DN. In addition, authors of DN studies might be unaware of the potential influence of RA on study results and conclusions. IMPACT: Improved reporting of COI/RA might improve credibility of results and help identify the various factors involved in complex interventions provided by physical therapists. Doing so could help optimize treatments for musculoskeletal pain disorders provided by physical therapists.

The meaning of regular participation in vigorous-intensity exercise among men with Parkinson's disease.

PURPOSE: To understand the meaning of regular participation in multiple types of vigorous-intensity exercise for those with Parkinson's disease (PD). MATERIALS AND METHODS: Using a qualitative phenomenological approach, in-depth individual interviews were conducted with eight male participants who engaged in at least two modes of vigorous-intensity exercise, including Rock Steady Boxing, about their experiences with exercise and the multifaceted role it played in their lives. Interview data were analyzed using systematic coding and organized into primary themes. RESULTS: Three primary themes emerged from the interview data: (1) the unique importance of social connections with others diagnosed with PD, (2) a sense of purpose, and (3) determination and confidence. Specifically, for those with a minimal history of engagement in exercise, regular participation in multiple types of vigorous-intensity exercise accompanied life-affirming social connections that served to boost feelings of hope and foster a clear sense of purpose in the face of disease. Participation in regular vigorous-intensity exercise fueled determination and confidence to engage in even more vigorous activities. CONCLUSIONS: Implications for rehabilitation practice include the importance of collaboration between health care professionals and community programs for people with PD. Promotion of group-based community activities, vigorous-intensity modes of exercise, and consideration of a patient's exercise history will be essential for the successful delivery of future services.IMPLICATIONS FOR REHABILITATIONSocial connections built through Rock Steady Boxing, a group exercise program, served as a catalyst for increasing hope, sense of purpose and motivation for people with Parkinson's disease;Vigorous-intensity exercise at Rock Steady Boxing fueled determination and confidence to engage in additional vigorous exercise regimens;Collaboration between health care providers and community partners is essential for long-term service provision for individuals with disability;Exercise history should be considered when making recommendations for physical activity.

Does a Sway-Based Mobile Application Predict Future Falls in People With Parkinson Disease?

OBJECTIVE: To determine whether Sway, a sway-based mobile application, predicts falls and to evaluate its discriminatory sensitivity and specificity relative to other clinical measures in identifying fallers in individuals with Parkinson disease (PD). DESIGN: Observational cross-sectional study. SETTING: Community. PARTICIPANTS: A convenience sample of subjects with idiopathic PD in Hoehn and Yahr levels I-III (N=59). INTERVENTIONS: Participants completed a balance assessment using Sway, the Movement Disorders Systems-Unified PD Rating Scale motor examination, Mini-BESTest, Activities-specific Balance Confidence (ABC) Scale, and reported 6-month fall history. Participants also reported falls for each of the following 6 months. Binomial logistic regression was used to identify significant predictors of future fall status. Cutoff scores, sensitivity, and specificity were based on receiver operating characteristic plots. MAIN OUTCOME MEASURES: Sway score. RESULTS: The most predictive logistic regression model included fall history, ABC Scale, and Sway (P<.001). This model explained 61% (Nagelkerke R2) of the variance in fall prediction and correctly classified 85% of fallers. However, only fall history and ABC Scale were statistically significant (P<.02). Participants were 32 times more likely to fall in the future if they fell in the past. The ABC Scale and Mini Balance Evaluation Systems Test (Mini-BESTest) demonstrated greater accuracy than Sway (area under the curve=0.76, 0.72, and 0.65, respectively). Cutoff scores to identify fallers were 85% for the ABC Scale and 21 of 28 for the Mini-BESTest. CONCLUSION: Sway did not improve the accuracy of predicting future fallers beyond common clinical measures and fall history.

Rate of Progression in Activity and Participation Outcomes in Exercisers with Parkinson's Disease: A Five-Year Prospective Longitudinal Study.

BACKGROUND: Rates of progression of motor symptoms and physical performance show declines between 2% and 7% annually in community samples with Parkinson's disease (PD). However, the effects of ongoing exercise behaviors on progression rates have not been considered. OBJECTIVE: The primary purpose of this prospective, longitudinal study was to examine the annual rates of progression in activity and participation measures over five years in community-based exercisers with PD. METHODS: A cohort of 55 regular exercisers with idiopathic PD was assessed at baseline and 1, 2, and 5 years. Regular exercise was defined as scores of 4-5 on the Stages for Readiness to Exercise Scale and a self-reported average of at least 60 minutes of exercise/week within six months of each testing session. Unadjusted and adjusted annual progression rates for activity and participation measures were calculated with a standardized equation of change from baseline. A linear mixed model with covariates of age at PD diagnosis and PD subtype was used to determine adjusted change scores. RESULTS: Annual progression rates for unadjusted and adjusted variables were similar, and none exceeded 1.7% across time points for this group of exercisers with PD. Older age at PD diagnosis significantly contributed to faster progression of walking and balance functions. A nonlinear trajectory of the PD progression was demonstrated across most activity and participation outcomes. CONCLUSIONS: Annual progression rates demonstrated by this sample of exercisers were lower than those previously reported for motor decline in general samples with PD. Assessing activity and participation outcomes longitudinally at interim time points was important for understanding the trajectory of change over time. The lower rates of progression in this study warrant further investigation into the long-term effects of exercise in PD.

Predictors of outcomes in exercisers with Parkinson disease: A two-year longitudinal cohort study.

BACKGROUND: Exercise may modify disease progression in persons with Parkinson disease (PD). OBJECTIVE: The purpose of this longitudinal cohort study was to determine factors that predict motor, activity, and participation-based outcomes over two years in exercisers with PD. METHODS: A convenience sample with idiopathic PD was included in the analysis [n = 74; mean age 66.7(8.4) years; male 54%; median months post diagnosis 69.0(76.0), median Hoehn and Yahr score 1.0(2.0)]. Exercise behaviors (minutes of exercise/week, peak rate of perceived exertion (RPE) and mode of exercise) and outcomes of impairment [grip strength], activity [10-meter walk test, functional reach test, activity specific balance confidence scale] and participation [Parkinson Disease Questionnaire-39] were assessed at baseline, 6, 12, 18 and 24 months. RESULTS: Using generalized estimating equations at least one exercise behavior was a significant predictor across most of the models (p≤0.026), with higher RPE predicting better outcomes in all activity and participation domains. Younger age, male gender and lower disease severity also significantly predicted better outcomes over time (p≤0.041). CONCLUSIONS: Exercise behaviors contributed to activity and participation-based outcomes over two years in exercisers with PD. Participation in high-intensity exercise programs may enhance maintenance of health and function over time in individuals with PD.

Physiological complexity of gait between regular and non-exercisers with Parkinson's disease.

BACKGROUND: Physiological complexity represents overall health of a system and its underlying capacity to adapt to stresses. The primary purpose of this study was to determine if physiological complexity of gait both ON and OFF anti-Parkinson medication differed between regular and non-exercisers with Parkinson's disease. METHODS: Twenty participants with idiopathic Parkinson's disease were enrolled in this cross-sectional study (regular exercisers n = 10, non-exercisers n = 10). Two data collection sessions were completed during a single visit, first after a 12-hour overnight withdrawal from anti-Parkinson medications (OFF), and again one-hour after taking anti-Parkinson medications (ON). During each session participants completed a 2-minute walking task at their preferred pace while wearing wireless inertial measurement units on each lower extremity segment (thigh, shank, foot). Multivariate multiscale entropy was calculated from the tri-axial accelerometer signals and converted to a complexity index for analysis. FINDINGS: Regular exercisers demonstrated significantly higher complexity indices ON and OFF anti-Parkinson medications compared to non-exercisers (ON F = 3.84 P = 0.02; OFF F = 3.61, P < 0.03). Regular exercisers did not significantly differ in complexity between OFF and ON states (most affected leg F = 0.15 P = 0.71; least affected leg F = 0.30 P = 0.60), but non-exercisers demonstrated significantly decreased complexity in the least affected leg OFF anti-Parkinson medications (F = 5.17 P < 0.04). INTERPRETATION: Enhanced gait complexity in the regular exercisers may indicate that ongoing exercise is a key ingredient contributing to health in persons with Parkinson's disease. Exercising on a regular basis with Parkinson's disease may augment one's ability to adapt to barriers encountered during gait regardless of medication state.

Physiological complexity of gait is decreased in individuals with chronic stroke.

Complexity represents the adaptability of the biological system, therefore the assessment of complexity during tasks such as walking may be particularly useful when attempting to better understand the recovery processes after stroke. The purpose of this study was to determine whether the complexity of lower extremity gait kinematics in persons with chronic hemiparesis due to stroke is different from that of individuals without disability during a gait task. The group of participants with chronic stroke exhibited reduced gait complexity across all body segments compared to those without disability. The decreased complexity of gait after stroke may represent diminished adaptability in the neuromotor system and may have significant implications when it comes to negotiating diverse environmental constraints and the ability to relearn pre-stroke gait patterns.

Application of 21-gene recurrence score results and ASTRO suitability criteria in breast cancer patients treated with intraoperative radiation therapy (IORT).

BACKGROUND: American Society for Radiation Oncology (ASTRO) suitability criteria for accelerated partial breast irradiation (APBI) and the 21-gene recurrence score (RS) were evaluated for prognostic and predictive benefit in IORT patients. METHODS: Outcomes of 184 patients completing IRB approved IORT protocol were retrospectively reviewed. Data included demographics, histopathology, RS, adjuvant therapy, locoregional (LRR) and distant recurrences (DR), and breast cancer-specific survival. RESULTS: There were 10 (5.4%) breast cancer recurrences, including one breast cancer-specific death. All 184 patients were classified by ASTRO suitability criteria (suitable: 64% (5 LRR), cautionary: 30% (3 LRR), unsuitable: 6.0% (1 LRR, 1 DR leading to death). RS were available in 114 estrogen receptor positive patients (<11: 22% (1 LRR), 11-25: 63% (1 LRR), 26-30: 9%, >30: 6%). Mean follow-up was 55 months. CONCLUSIONS: ASTRO suitability criteria for APBI and RS were useful in making prognostic and therapeutic recommendations for patients considering IORT.

Reliability and validity of the Sway Balance mobile application for measurement of postural sway in people with Parkinson disease.

BACKGROUND: The emergence of mobile technology allows the examination of balance through direct measures of postural sway in a cost-effective, convenient and portable fashion. However, there is insufficient evidence for use in populations with neurologic conditions. OBJECTIVES: 1) To determine the test-retest reliability of the Sway Balance™ mobile application in measuring postural sway in individuals with Parkinson disease, 2) To examine the concurrent validity of Sway Balance™ with inertial measurement units and 3) To determine if Sway Balance™ scores can predict disease severity. METHODS: Thirty subjects with early stage idiopathic Parkinson disease completed three trials of two Sway Balance™ protocols while postural sway was simultaneously measured by two inertial measurement units and Sway Balance™, then repeated testing one week later. RESULTS: Sway Balance demonstrated high test-retest reliability for both protocols (ICC = 0.72 and 0.92) and good to excellent inverse correlation with the inertial measurement units across both protocols (ρ= -0.61- -0.92; p < 0.001). Sway Balance™ did not accurately predict disease severity. CONCLUSION: Sway Balance™ demonstrates strong test-retest reliability and concurrent validity with measures from inertial measurement units. Questions remain regarding the ability of Sway Balance™ to accurately characterize balance of individuals who demonstrate difficulty maintaining the test condition.

Scale Formation Under Blended Phosphate Treatment for a Utility With Lead Pipes.

US corrosion control practice often assumes that the orthophosphate component of blended phosphate corrosion inhibitors causes the formation of low-solubility lead-orthophosphate solids that control lead release into drinking water. This study identified the solids that formed on the interior surface of a lead service line and a galvanized steel pipe excavated from a system using a proprietary blended phosphate chemical. The scale was analyzed by X-ray diffraction, X-ray fluorescence, and scanning electron microscopy/energy dispersive spectroscopy. Instead of crystalline lead-orthophosphate solids, a porous amorphous layer rich in aluminum, calcium, phosphorus, and lead was observed at the lead pipe scale-water interface. Thus, the mechanism inhibiting lead release into the water was not a thermodynamically predictable passivating lead-orthophosphate scale, but rather an amorphous barrier deposit that was possibly vulnerable to disturbances. Galvanized pipe scales showed relatively crystalline iron and zinc compounds, with additional surface deposition of aluminum, phosphorus, calcium, and lead.

Are the average gait speeds during the 10meter and 6minute walk tests redundant in Parkinson disease?

We investigated the relationships between average gait speed collected with the 10Meter Walk Test (Comfortable and Fast) and 6Minute Walk Test (6MWT) in 346 people with Parkinson disease (PD) and how the relationships change with increasing disease severity. Pearson correlation and linear regression analyses determined relationships between 10Meter Walk Test and 6MWT gait speed values for the entire sample and for sub-samples stratified by Hoehn & Yahr (H&Y) stage I (n=53), II (n=141), III (n=135) and IV (n=17). We hypothesized that redundant tests would be highly and significantly correlated (i.e. r>0.70, p<0.05) and would have a linear regression model slope of 1 and intercept of 0. For the entire sample, 6MWT gait speed was significantly (p<0.001) related to the Comfortable 10 Meter Walk Test (r=0.75) and Fast 10Meter Walk Test (r=0.79) gait speed, with 56% and 62% of the variance in 6MWT gait speed explained, respectively. The regression model of 6MWT gait speed predicted by Comfortable 10 Meter Walk gait speed produced slope and intercept values near 1 and 0, respectively, especially for participants in H&Y stages II-IV. In contrast, slope and intercept values were further from 1 and 0, respectively, for the Fast 10Meter Walk Test. Comfortable 10 Meter Walk Test and 6MWT gait speeds appeared to be redundant in people with moderate to severe PD, suggesting the Comfortable 10 Meter Walk Test can be used to estimate 6MWT distance in this population.

Body weight-supported treadmill training vs. overground walking training for persons with chronic stroke: a pilot randomized controlled trial.

OBJECTIVE: To compare the effects of body weight-supported treadmill training and overground walking training when matched for task and dose (duration/frequency/intensity) on improving walking function, activity, and participation after stroke. DESIGN: Single-blind, pilot randomized controlled trial with three-month follow-up. SETTINGS: University and community settings. SUBJECTS: A convenience sample of participants (N = 20) at least six months post-stroke and able to walk independently were recruited. INTERVENTIONS: Thirty-minute walking interventions (body weight-supported treadmill training or overground walking training) were administered five times a week for two weeks. Intensity was monitored with the Borg Rating of Perceived Exertion Scale at five-minute increments to maintain a moderate training intensity. MAIN MEASURES: Walking speed (comfortable/fast 10-meter walk), walking endurance (6-minute walk), spatiotemporal symmetry, and the ICF Measure of Participation and ACTivity were assessed before, immediately after, and three months following the intervention. RESULTS: The overground walking training group demonstrated significantly greater improvements in comfortable walking speed compared with the body weight-supported treadmill training group immediately (change of 0.11 m/s vs. 0.06 m/s, respectively; p = 0.047) and three months (change of 0.14 m/s vs. 0.08 m/s, respectively; p = 0.029) after training. Only the overground walking training group significantly improved comfortable walking speed (p = 0.001), aspects of gait symmetry (p = 0.032), and activity (p = 0.003) immediately after training. Gains were maintained at the three-month follow-up (p < 0.05) for all measures except activity. Improvements in participation were not demonstrated. CONCLUSION: Overgound walking training was more beneficial than body weight-supported treadmill training at improving self-selected walking speed for the participants in this study.

Epigenetic regulation of the miR142-3p/interleukin-6 circuit in glioblastoma.

Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feedback-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target.

Colon cancer stem cells resist antiangiogenesis therapy-induced apoptosis.

Antiangiogenesis is an efficient therapy for eliminating colon cancers, but because of recurrence it remains only palliative. We hypothesized that certain populations of tumor cells resist antiangiogenesis-induced apoptosis and explored the underlying mechanism. We demonstrated that the CD133(+) population of cells in colon cancer is resistant to anti-angiogenesis therapy. Additionally, we identified an anti-apoptotic signaling pathway responsible for this resistance involving PP2A, p38MAPK, MAPKAPK2, and Hsp27. Thus, this pathway may offer a new avenue to develop target therapy for colorectal cancer.

Survival of cancer stem cells under hypoxia and serum depletion via decrease in PP2A activity and activation of p38-MAPKAPK2-Hsp27.

Hypoxia and serum depletion are common features of solid tumors that occur upon antiangiogenesis, irradiation and chemotherapy across a wide variety of malignancies. Here we show that tumor cells expressing CD133, a marker for colorectal cancer initiating or stem cells, are enriched and survive under hypoxia and serum depletion conditions, whereas CD133- cells undergo apoptosis. CD133+ tumor cells increase cancer stem cell and epithelial-mesenchymal transition properties. Moreover, via screening a panel of tyrosine and serine/threonine kinase pathways, we identified Hsp27 is constitutively activated in CD133+ cells rather than CD133- cell under hypoxia and serum depletion conditions. However, there was no difference in Hsp27 activation between CD133+ and CD133- cells under normal growth condition. Hsp27 activation, which was mediated by the p38MAPK-MAPKAPK2-Hsp27 pathway, is required for CD133+ cells to inhibit caspase 9 and 3 cleavage. In addition, inhibition of Hsp27 signaling sensitizes CD133+ cells to hypoxia and serum depletion -induced apoptosis. Moreover, the antiapoptotic pathway is also activated in spheroid culture-enriched CD133+ cancer stem cells from a variety of solid tumor cells including lung, brain and oral cancer, suggesting it is a common pathway activated in cancer stem cells from multiple tumor types. Thus, activation of PP2A or inactivation of the p38MAPK-MAPKAPK2-Hsp27 pathway may develop new strategies for cancer therapy by suppression of their TIC population.

The crosstalk of mTOR/S6K1 and Hedgehog pathways.

Esophageal adenocarcinoma (EAC) is the most prevalent esophageal cancer type in the United States. The TNF-α/mTOR pathway is known to mediate the development of EAC. Additionally, aberrant activation of Gli1, downstream effector of the Hedgehog (HH) pathway, has been observed in EAC. In this study, we found that an activated mTOR/S6K1 pathway promotes Gli1 transcriptional activity and oncogenic function through S6K1-mediated Gli1 phosphorylation at Ser84, which releases Gli1 from its endogenous inhibitor, SuFu. Moreover, elimination of S6K1 activation by an mTOR pathway inhibitor enhances the killing effects of the HH pathway inhibitor. Together, our results established a crosstalk between the mTOR/S6K1 and HH pathways, which provides a mechanism for SMO-independent Gli1 activation and also a rationale for combination therapy for EAC.