Study protocol for 'the effects of multimodal training of cognitive and/or physical functions on cognition and physical fitness of older adults: a cluster randomized controlled trial'.

BACKGROUND: The elderly population worldwide is increasing exponentially which will be associated with more people suffering from cognition and fitness declines. The well-established benefits of exercise training for the elderly's cognitive and physical functioning have been observed. However, the amalgamated effect of combining cognitive and physical exercises on the older adults' cognitive functions, physical fitness, or psycho-related health remains unclear. Thus, this study protocol was planned to conduct different combinations of cognitive and/or physical training interventions to community-dwelling older adults and expected to see the multifaceted effects of the varied combination of training on their health. METHODS: This study is a cluster randomized controlled trial (CRCT). A total of 285 older adults (age ≥ 60) from twenty elderly centres as clusters will be randomly selected and assigned to intervention groups (IGs, n = 16) or control groups (CGs, n = 4). Each IG will be randomly assigned to one of the four combinations of three training modes that include cognitive (A), physical (B), and combined cognitive and physical training (CCPT, i.e. C), namely Mixed ABC, A + B, C + A, B + C. The intervention will last for 4 months in which the training is conducted for 16 sessions, 2 sessions per week, and 60 min per session. Four repeated assessments (pre-test, two post-training tests after 2 months and 4 months, and a follow-up test) will be conducted. The CG will only receive the four repeated assessments but no intervention. The outcome measures include cognitive tests (tests of execution, memory, and psych-social status), physical fitness, and dynamic balance tests. DISCUSSION: This study will provide substantial evidence that the integrated format of cognitive and physical exercises training will have higher cognition and fitness impact than the single training modes, and all these mixed modalities will have greater positive outcomes than the control condition. If the effectiveness is proven, the intervention can be further explored and extended to the nation so that many more elderly would be benefited. TRIAL REGISTRATION: The trial has been registered in the ClinicalTrials.gov in U.S. NIH (ID: NCT04727450 , date: January 27, 2021).

Effects of traditional Cantonese opera songs on Cantonese-speaking, community-dwelling older adults' cognitive and psychological function, well-being, and health.

Objectives: Experiencing multi-sensory cognitive stimulation through the enjoyment of Cantonese opera songs, with their lively rhythms, familiar folk tales, meaningful lyrics and pleasant scenarios, has the potential to increase neuroplasticity and prevent cognitive decline.Methods: This prospective pre- and post-test quasi-experimental randomised controlled trial design study aimed to explore the social benefits of older adults' active participation in practising Cantonese opera songs as compared with passive participation (as an audience) and a non-interventional control group on cognitive function psychological function, functional independence, well-being and health.Results: By recruiting a group of older adults who were receiving day activities social service in Hong Kong. Thirty participants were randomly allocated to active participation in Cantonese opera (ACO). They participated in practising Cantonese opera songs. Thirty-four participants were assigned to passive participation in Cantonese opera (PCO). They received passive intervention by listening to and appreciating the opera songs as a social event. Thirty-one participants were used as a control group and received no similar training. (Results) ACO caused a positive change in cognitive function as compared to PCO and to no intervention, which implies that active learning and practise of opera songs benefits global cognitive function. The psychological function of the participants in the PCO group showed an elevated positive affect and a reduced negative affect. A statistically significant difference was noted in the time effect among the physical domains of health status, functional independence and well-being of participants who underwent Cantonese opera intervention.

Self-reported prospective memory after stroke.

Prospective Memory (PM) is the memory for completing future intentions. This study aimed to compare self-reported PM of individuals with stroke to healthy controls, to determine if PM is impaired after stroke. Additionally, self-reported PM for individuals with stroke was compared to significant-other reports, ascertaining a level of self-awareness of PM function. Twenty-eight individuals with stroke, 25 significant-others, and 27 healthy controls completed the Brief Assessment of PM (BAPM) and the Prospective and Retrospective Memory Questionnaire (PRMQ) as part of a larger study. Individuals with stroke reported significantly more Basic Activities of Daily Living (BADL) PM failures compared to controls on Part A of the BAPM. On Part B, individuals with stroke reported BADL PM failures to be less problematic/important than controls, suggesting a lack of self-awareness into the consequences of PM failure. Individuals with stroke also reported significantly more PM and RM failures compared to controls on the PRMQ. No significant differences were found between individuals with stroke and their significant-others on both the BAPM and PRMQ. Results of this study helped to clarify the previous research and highlighted that individuals with stroke reported more PM failures than controls but underestimated the importance of such memory lapses.

Virtual reality-based cognitive training for drug abusers: A randomised controlled trial.

Non-pharmacological means are being developed to enhance cognitive abilities in drug abusers. This study evaluated virtual reality (VR) as an intervention tool for enhancing cognitive and vocational outcomes in 90 young ketamine users (KU) randomly assigned to a treatment group (virtual reality group, VRG; tutor-administered group, TAG) or wait-listed control group (CG). Two training programmes with similar content but different delivery modes (VR-based and manual-based) were applied using a virtual boutique as a training scenario. Outcome assessments comprised the Digit Vigilance Test, Rivermead Behavioural Memory Test, Wisconsin Cart Sorting Test, work-site test and self-efficacy pre- and post-test and during 3- and 6-month follow-ups. The VRG exhibited significant improvements in attention and improvements in memory that were maintained after 3 months. Both the VRG and TAG exhibited significantly improved vocational skills after training which were maintained during follow-up, and improved self-efficacy. VR-based cognitive training might target cognitive problems in KU.

Bibliometric study of research productivity in occupational therapy and physical therapy/physiotherapy in four Western countries and five Asian countries/regions.

INTRODUCTION: High-quality research is the foundation of occupational therapy and physical therapy/physiotherapy. A bibliometric study on the research productivity of occupational therapy and physical therapy/physiotherapy scholars in different Western and Asian countries/regions could provide a snapshot of current research achievement in rehabilitation science. METHOD: On the basis of an understanding of the leading role of rehabilitation research in Western countries and a recognition of achievements made by Asian occupational therapy and physical therapy/physiotherapy scholars, the current bibliometric study examined the research productivity of occupational therapy and physical therapy/physiotherapy professors and associate professors from four Western countries (Australia, Canada, the United States and the United Kingdom) and five Asian countries/regions (Hong Kong, Japan, Taiwan, Singapore and South Korea). The h-indices of these scholars were retrieved online and aggregated to quantify the research productivity of institutions and countries/regions. RESULTS: Australia, Canada, Hong Kong and the United States were identified as countries/regions with higher research productivity in occupational therapy and physical therapy/physiotherapy. The institutions were ranked on the basis of the median h-indices of their professors and associate professors; the top 20 productive institutions with occupational therapy programmes had a median h-index of 17.5 or higher, whereas the benchmark of the top 20 institutions with physical therapy/physiotherapy programmes was 25. CONCLUSION: Professors and associate professors in Australia, Canada, Hong Kong and the United States are productive in occupational therapy and physical therapy/physiotherapy research. The number of faculty members and university connections are regarded as important for research achievement. Recommendations for various levels of collaboration are provided.

Validation of the virtual-reality prospective memory test (Hong Kong Chinese version) for individuals with first-episode schizophrenia.

This study was performed to examine the psychometric properties of a Virtual-Reality Prospective Memory Test (Hong Kong Chinese version; VRPMT-CV). The VRPMT was administered to 44 individuals with first-episode schizophrenia. The test was administered again 2 weeks later to establish test-retest reliability. The concurrent validity of the VRPMT was evaluated by examining the correlations between the VRPMT score and the score on the Chinese version of the Cambridge Prospective Memory Test (CAMPROMPT-CV). The performance of individuals with schizophrenia on the VRPMT was also compared with that of 42 healthy control subjects to examine the test's sensitivity and specificity. The intraclass correlation for test-retest reliability of the total VRPMT-CV score was 0.78 (p = .005). A significant correlation was found between the total VRPMT-CV score and the total CAMPROMPT-CV score (r = 0.90; p < .001). Comparison with the healthy control subjects revealed that the total VRPMT-CV score was a sensitive (92.9%) and specific (75%) measure of prospective memory deficits in individuals with schizophrenia. The VRPMT-CV is an assessment of prospective memory that has good construct validity, test-retest reliability, sensitivity and specificity in the context of first-episode schizophrenia.

Self-report prospective memory problems in people with stroke.

BACKGROUND AND PURPOSE: Prospective memory (PM) is a common problem which can limit performance of basic and instrumental activities of daily living in patients with stroke. This study compared self-report PM failures between older and younger people with stroke, examined differences in perceptions of PM failures between people with stroke and relatives, relationships between these PM failures and functional performance. METHODS: A total of 105 patients with stroke, 65 relatives and 112 healthy controls were recruited. Both the patients with stroke and controls were further divided into an older (age > 55 years) and a younger (age ≤ 55 years) group. Data for patients with stroke and relatives were obtained via the Brief Assessment of Prospective Memory (BAPM), Basic Activity of Daily Living (BADL) related Modified Barthel Index (MBI) and Lawton Instrumental Activities of Daily Living (Lawton IADL) Scale. Healthy controls' data were also collected. RESULTS: The older stroke group had significantly higher BAPM total scores and BADL and IADL sub-scale scores than the younger group. Difference in perceptions of the patients' self-report of PM failures and their relatives' report was significant for the IADL sub-scale. Self-report of PM failure was significantly related to functional BADL and IADL measures. CONCLUSIONS: Results highlight the impact of PM failures in patients with stroke and their assessment, management and rehabilitation of these patients.

Validation of the Cambridge Prospective Memory Test (Hong Kong Chinese version) for people with stroke.

This study aimed to develop and evaluate a Hong Kong Chinese version of the Cambridge Prospective Memory Test (CAMPROMPT-HKCV). Thirty-three subjects at least one year post-stroke participated in the study. They were simultaneously rated on version A of the CAMPROMPT-HKCV by two testers to establish its internal consistency and inter-rater reliability. Raters used the parallel versions of the test (A and B), in rating 10 patients within 2 weeks to establish the parallel form reliability. Another 10 were also assessed on the same day using both version A of the CAMPROMPT-HKCV and the Rivermead Behavioural Memory Test-Chinese version (RBMT-CV) to establish concurrent validity. A new group of 40 stroke patients and 44 healthy controls was recruited to establish its sensitivity and specificity. Results indicated that test-retest reliability on time-based, event-based and total scores, and inter-rater reliability for versions A and B of the test were high. Cronbach's alpha of the event-based score was higher than that of the time-based score. The reliability and concurrent validity of the parallel forms were established. There was a significant difference in performance on CAMPROMPT-HKCV (version A) between the stroke group and the healthy control group. ROC analysis showed that the ability of the cut-off CAMPROMPT-HKCV (total score) to differentiate PM problems was 20.5 (out of 36) with sensitivity at 95.5% and specificity at 55.9%. Further study in developing stratified norms across different age groups in Chinese-speaking stroke patients is recommended.

Evaluation of a virtual reality prospective memory task for use with individuals with severe traumatic brain injury.

The current study aimed to evaluate the sensitivity, convergent validity and ecological validity of a newly developed virtual reality prospective memory (PM) task (i.e., the Virtual Reality Shopping Task; VRST) for use with individuals with traumatic brain injury (TBI). Thirty individuals with severe TBI and 24 uninjured adults matched on age, gender and education level were administered the VRST, a lexical decision PM task (LDPMT), an index of task-friendliness and a cognitive assessment battery. Significant others rated disruptions in the TBI participants' occupational activities, interpersonal relationships and independent living skills. The performance of the TBI group was significantly poorer than that of controls on event-based PM as measured by the LDPMT, and on time- and event-based PM as measured by the VRST. Performance on the VRST significantly predicted significant others' ratings of patients' occupational activities and independent living skills. The VRST was rated as significantly more reflective of an everyday activity, interesting and was afforded a higher recommendation than the LDPMT. For the TBI group, event and total PM performance on the VRST significantly correlated with performance on measures of mental flexibility and verbal fluency, and total PM performance correlated with verbal memory. These results provide preliminary but promising evidence of the sensitivity, as well as the convergent and ecological validity of the VRST.

An AI-empowered indoor digital contact tracing system for COVID-19 outbreaks in residential care homes.

An AI-empowered indoor digital contact-tracing system was developed using a centralized architecture and advanced low-energy Bluetooth technologies for indoor positioning, with careful preservation of privacy and data security. We analyzed the contact pattern data from two RCHs and investigated a COVID-19 outbreak in one study site. To evaluate the effectiveness of the system in containing outbreaks with minimal contacts under quarantine, a simulation study was conducted to compare the impact of different quarantine strategies on outbreak containment within RCHs. The significant difference in contact hours between weekdays and weekends was observed for some pairs of RCH residents and staff during the two-week data collection period. No significant difference between secondary cases and uninfected contacts was observed in a COVID-19 outbreak in terms of their demographics and contact patterns. Simulation results based on the collected contact data indicated that a threshold of accumulative contact hours one or two days prior to diagnosis of the index case could dramatically increase the efficiency of outbreak containment within RCHs by targeted isolation of the close contacts. This study demonstrated the feasibility and efficiency of employing an AI-empowered system in indoor digital contact tracing of outbreaks in RCHs in the post-pandemic era.

Prospective memory impairment and its implications for community living skills in bipolar disorder.

OBJECTIVE: Prospective memory (PM) refers to the ability to undertake intended actions in the future. The functional significance of PM in bipolar disorder (BD) has not yet been investigated. This study examined PM impairment and its role in community living skills in clinically stable individuals with BD. METHODS: Seventy-six individuals with BD and 44 healthy individuals were assessed with the Chinese version of the Cambridge Prospective Memory Test. Socio-demographic characteristics, retrospective memory (RM; the ability to recall or recognize past information), and intelligence were also measured in all participants. The clinical condition and community living skills of patients with BD were rated independently with standardized instruments. RESULTS: Patients with BD showed PM impairment and their PM total scores independently predicted the level of community living skills in regression analyses. In follow-up analyses, the contribution was found to be accounted for by the time-based PM scores. CONCLUSIONS: Given the expanding body of research on the utility of PM in predicting functioning, these findings further support the role of PM in community living skills in individuals with BD. The results suggest that PM training might be an integral part of clinical rehabilitation devised for individuals with BD.

The effectiveness of artificial intelligent 3-D virtual reality vocational problem-solving training in enhancing employment opportunities for people with traumatic brain injury.

BACKGROUND: People with traumatic brain injury (TBI) often experience cognitive deficits in attention, memory, executive functioning and problem-solving. The purpose of the present research study was to examine the effectiveness of an artificial intelligent virtual reality (VR)-based vocational problem-solving skill training programme designed to enhance employment opportunities for people with TBI. METHOD: This was a prospective randomized controlled trial (RCT) comparing the effectiveness of the above programme with that of the conventional psycho-educational approach. Forty participants with mild (n = 20) or moderate (n = 20) brain injury were randomly assigned to each training programme. Comparisons of problem-solving skills were performed with the Wisconsin Card Sorting Test, the Tower of London Test and the Vocational Cognitive Rating Scale. RESULTS: Improvement in selective memory processes and perception of memory function were found. Across-group comparison showed that the VR group performed more favourably than the therapist-led one in terms of objective and subjective outcome measures and better vocational outcomes. CONCLUSIONS: These results support the potential use of a VR-based approach in memory training in people with MCI. Further VR applications, limitations and future research are described.

A Health App for Post-Pandemic Years (HAPPY) for people with physiological and psychosocial distress during the post-pandemic era: Protocol for a randomized controlled trial.

Objective: This article describes a protocol for a randomized controlled trial to evaluate the effects of a three-level Health App for Post-Pandemic Years (HAPPY) on alleviating post-pandemic physiological and psychosocial distress. Methods: Convenience and snowball sampling methods will be used to recruit 814 people aged 18+ with physiological and/or psychosocial distress. The experimental group will receive a 24-week intervention consisting of an 8-week regular supervision phase and a 16-week self-help phase. Based on their assessment results, they will be assigned to receive interventions on mindfulness, energy conservation techniques, or physical activity training. The waitlist control group will receive the same intervention in Week 25. The primary outcome will be changes in psychosocial distress, measured using the Kessler Psychological Distress Scale (K10). Secondary outcomes will include changes in levels of fatigue (Chinese version of the Brief Fatigue Inventory), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index), pain intensity (Numeric Rating Scale), positive appraisal (Short version of the 18-item Cognitive Emotion Regulation Questionnaire), self-efficacy (Chinese version of the General Self-efficacy Scale), depression and anxiety (Chinese version of the 21-item Depression Anxiety Stress Scale), and event impact (Chinese version of the 22-item Impact of Event Scale-Revised). All measures will be administered at baseline (T0), Week 8 after the supervision phase (T1), and 24 weeks post-intervention (T2). A generalized estimating equations model will be used to examine the group, time, and interaction (Time × Group) effect of the interventions on the outcome assessments (intention-to-treat analysis) across the three time points, and to compute a within-group comparison of objective physiological parameters and adherence to the assigned interventions in the experimental group. Conclusions: The innovative, three-level mobile HAPPY app will promote beneficial behavioral strategies to alleviate post-pandemic physiological and psychosocial distress. Trial registration: ClinicalTrials.gov, NCT05459896. Registered on 15 July 2022.

Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: a pilot study.

BACKGROUND: Older adults with questionable dementia are at risk of progressing to dementia, and early intervention is considered important. The present study investigated the effectiveness of a virtual reality (VR)-based memory training for older adults with questionable dementia. METHODS: A pre-test and post-test design was adopted. Twenty and 24 older adults with questionable dementia were randomly assigned to a VR-based and a therapist-led memory training group, respectively. Primary outcome measures included the Multifactorial Memory Questionnaire and Fuld Object Memory Evaluation. RESULTS: Both groups demonstrated positive training effects, with the VR group showing greater improvement in objective memory performance and the non-VR group showing better subjective memory subtest results in the Multifactorial Memory Questionnaire. CONCLUSION: The use of VR seems to be acceptable for older adults with questionable dementia. Further study on the effect of educational background and memory training modality (visual, auditory) is warranted.

Information Communication Technology as Instrumental Activities of Daily Living for Aging-in-Place in Chinese Older Adults With and Without Cognitive Impairment: The Validation Study of Advanced Instrumental Activities of Daily Living Scale.

Background: The capability in applying information communication technology (ICT) is crucial to the functional independence of older peoples of community living nowadays. The proper assessment of individuals' capability of ICT application is the corner stone for the future development of telemedicine in our aging population. Methods: With the recruitment of 300 participants of different functional and social background in home-living, hostel-living, and care-and-attention home living; and through assessing the ability of individuals in instrumental activities of daily living and cognitive assessments, this study aimed at capturing the content validity and construct validity of the Advanced Instrumental Activities of Daily Living (AIADL scale). In addition, this study assess the ability of older peoples in applying ICT and how the functional and social background affects their independence in aging-in-place. Results: The AIADL scale showed good test-retest reliability and good-to-excellent internal consistency. To determine if items of the AIADL scale measure various aspects of community living, exploratory factor analysis revealed a two-factor structure with "home living and management" and "community living". Validity analysis with the known-groups method showed a high overall accuracy of prediction of individuals' capability of independent living in the community. Conclusions: The AIADL scale is a valid and reliable instrument to assess the ability of older adults in handling ICT as part of their instrumental activities in daily living. The scale can reflect capability of older peoples in applying ICT. This instrument can serve as a reference in measuring readiness of individuals in receiving telemedicine and their ability of aging-in-place.

Development of the Brief Assessment of Prospective Memory (BAPM) for use with traumatic brain injury populations.

Impairment of prospective memory (PM) is a common problem following traumatic brain injury (TBI) which can affect functional outcomes. PM failures in everyday life can be assessed using self-report questionnaires; however, existing measures tend to be lengthy, which may be problematic for individuals with fatigue and other cognitive impairments. This study aimed to develop a short form of the Comprehensive Assessment of Prospective Memory (CAPM) and examine its psychometric properties. Using theoretical and statistical considerations, the number of items on the CAPM was reduced to 16 including equal numbers representing the basic activities of daily living (BADL) and instrumental activities of daily living (IADL) subscales. The psychometric properties of the new measure, named the Brief Assessment of Prospective Memory (BAPM), were examined by secondary analysis of data from two samples of community dwelling adults (aged 17 to 91 years, n = 527, and 15 to 60 years, n = 95) with no history of brain injury, and a sample of rehabilitation patients with moderate to severe TBI (n = 45). Results indicate that the BAPM has a robust factor structure, strong agreement with the original CAPM, acceptable internal consistency and test-retest reliability, and evidence of criterion-related validity with psychosocial integration as the point of reference for people with TBI.

Validation of the Intelligent Cognitive Assessment System (ICAS) for stroke survivors.

PRIMARY OBJECTIVE: To investigate the internal consistency, test-re-test reliability of an Intelligent Cognitive Assessment System (ICAS) and its optimal cut-off score for stroke patients with or without cognitive impairment. METHOD: A prospective cohort study design was adopted. Sixty-six post-stroke patients of aged 60 or above were recruited. They were screened by the Chinese version of Mini Mental State Examination (MMSE-CV) and assessed by the Intelligent Cognitive Assessment System (ICAS) consisting of 65 testing items which could be presented at a level according to stroke patient's response. It was administered to examine the internal consistency and test-re-test reliability (by repeating within a 7-day interval). The optimal cut-off score to screen stroke patients having cognitive impairment was determined by the receiver operating characteristics (ROC) curve. RESULTS: The internal consistency of the ICAS (Cronbach's alpha = 0.878) and its test-re-test reliability (rho = 0.789; p < 0.001) were demonstrated. The cut-off score for the ICAS to determine cognitive impairment was found to be 3.02, with a sensitivity of 80.5% and specificity of 96%. CONCLUSION: Preliminary results suggested that ICAS was a valid and reliable cognitive screening tool for stroke survivors. The ICAS can be further developed by studying its norms for stroke patients. It is also programmable for potential application to different countries by changing ICAS to other language versions and including other culturally relevant content.

Systematic prediction of human membrane receptor interactions.

Membrane receptor-activated signal transduction pathways are integral to cellular functions and disease mechanisms in humans. Identification of the full set of proteins interacting with membrane receptors by high-throughput experimental means is difficult because methods to directly identify protein interactions are largely not applicable to membrane proteins. Unlike prior approaches that attempted to predict the global human interactome, we used a computational strategy that only focused on discovering the interacting partners of human membrane receptors leading to improved results for these proteins. We predict specific interactions based on statistical integration of biological data containing highly informative direct and indirect evidences together with feedback from experts. The predicted membrane receptor interactome provides a system-wide view, and generates new biological hypotheses regarding interactions between membrane receptors and other proteins. We have experimentally validated a number of these interactions. The results suggest that a framework of systematically integrating computational predictions, global analyses, biological experimentation and expert feedback is a feasible strategy to study the human membrane receptor interactome.

Self-appraised, informant-reported, and objective memory and cognitive function in mild cognitive impairment.

BACKGROUND/AIM: The current knowledge of how self-appraised memory and cognitive function relates to informant reports and neuropsychological performances in mild cognitive impairment (MCI) is limited. METHODS: Sixty-nine older community-dwelling subjects with MCI and 86 adults with normal cognition (NC) were evaluated on self-appraised (Multifactorial Memory Questionnaire) and objective performance of memory and cognitive function (Mini-Mental State Examination, Fuld Object Memory Evaluation, Digit Span tests, Rivermead Behavioral Memory Test). Informant ratings on the subjects' cognitive and memory functioning (Informant Questionnaire on Cognitive Decline in the Elderly) were also obtained. The two groups (MCI, NC) did not significantly differ in mean age (79 +/- 5.29 vs. 77 +/- 5.33) and mean years of education (2.8 +/- 3.03 vs. 3.7 +/- 4.18). RESULTS: Self-appraised satisfaction and ability of memory and cognitive functions did not correlate with informant reports and neuropsychological performances, but self-reported strategy use correlated with list recall and everyday memory tests in MCI. CONCLUSION: Persons with MCI may show signs of diminished awareness towards their subtle impairments of memory and cognitive function, as indicated by informant reports and neuropsychological tests.

Constitutive activation of signal transducer and activator of transcription 5 contributes to tumor growth, epithelial-mesenchymal transition, and resistance to epidermal growth factor receptor targeting.

PURPOSE: Signal transducer and activator of transcription 5 (STAT5) is activated in squamous cell carcinoma of the head and neck (SCCHN), where targeting of STAT5 inhibits tumor growth in vitro and in vivo. The role of STAT5 activation in carcinogenesis, tumor progression, and response to therapy remains incompletely understood. In this study, we investigated the effects of STAT5 activation on squamous epithelial carcinogenesis and response to therapy. EXPERIMENTAL DESIGN: The functional consequences of STAT5 activation in squamous epithelial carcinogenesis were examined using cells derived from normal (Het-1A) and transformed mucosal epithelial cells engineered to express constitutive-active mutants of STAT5. RESULTS: The growth rate of stable clones derived from both normal and transformed squamous epithelial cells expressing the constitutive-active STAT5 was increased. In SCCHN xenografts, tumor volumes were increased in constitutive-active STAT5 mutant cells compared with vector-transfected controls. Constitutive activation of STAT5 significantly increased cell migration and invasion through Matrigel, as well as the transforming efficiency of SCCHN cells in vitro, as assessed by soft agar assays. The constitutive-active STAT5 clones derived from SCCHN cells showed changes consistent with an epithelial-mesenchymal transition including decreased expression of E-cadherin and increased vimentin in comparison with control transfectants. In these cells, STAT5 activation was associated with resistance to cisplatin-mediated apoptosis and growth inhibition induced by the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib. CONCLUSIONS: These results suggest that constitutive STAT5 signaling enhances tumor growth, invasion, and epithelial-to-mesenchymal transition in squamous epithelial carcinogenesis and may contribute to resistance to epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy.