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Author(s): V. Wood [1]; R. Gwilliam [1]; M.-A. Rajandream (corresponding author) [1]; M. Lyne [1]; R. Lyne [1]; A. Stewart [2]; J. Sgouros [2]; N. Peat [3]; J. Hayles [3]; [...]

Author(s): V. Wood; R. Gwilliam; M.-A. Rajandream; M. Lyne; R. Lyne; A. Stewart; J. Sgouros; N. Peat; J. Hayles; S. Baker; D. Basham; S. Bowman; K. Brooks; D. Brown; S. [...]

Prehabilitation has been shown to improve outcomes for patients undergoing major surgery; benefits include reductions in length of hospital stay and postoperative complications. Multimodal prehabilitation programmes lead to improved patient engagement and experience. This report describes implementation of a personalised multimodal prehabilitation programme for patients awaiting colorectal cancer surgery. We aim to highlight the successes, challenges and future direction of our programme.Patients listed for colorectal cancer surgery were referred for initial prehabilitation assessment. The prehabilitation group were assessed by specialist physiotherapists, dieticians and psychologists. An individualised programme was developed for each patient, aiming to optimise preoperative functional capacity and enhance physical and psychological resilience. Clinical primary outcome measures were recorded and compared with contemporaneous controls. For those undergoing prehabilitation, a set of secondary functional, nutritional and psychological outcomes were recorded at initial assessment and on completion of the programme.61 patients were enrolled in the programme from December 2021 to October 2022. 12 patients were excluded as they received less than 14 days prehabilitation or had incomplete data. The remaining 49 patients received a median duration of 24 days prehabilitation (range 15-91 days). The results show statistically significant improvements in the following functional outcome measures after prehabilitation: Rockwood scores, maximal inspiratory pressures, International Physical Activity Questionnaire Score and Functional Assessment of Chronic Illness - Fatigue Score. There was a lower postoperative complication rate in the prehabilitation group when compared with a control group (50% vs 67%).This quality improvement project has 3 Plan-Do-Study-Act (PDSA) cycles. PDSA 1 demonstrates prehabilitation can be successfully imbedded within a colorectal surgical unit and that patients are grateful for the service. PDSA 2 provides the project's first complete data set and demonstrates functional improvements in patients undergoing prehabilitation. The third PDSA cycle is ongoing and aims to refine the prehabilitation interventions and improve clinical outcomes for patients undergoing colorectal cancer surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer., Methods: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months., Results: A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m 2 ). The median time since diagnosis was 34 months (IQR 7-54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen's d =  - 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1-3) and 67% (months 3-6). Modelling results for overall physical activity scores showed no significant main effect for the group (p-value = 0.25) or for time (p-value = 0.24)., Conclusion: In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed., Trial Registration: The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015., (© 2023. The Author(s).)

The impact of using exercise as a non-pharmacological intervention in patients with cancer receiving immune checkpoint inhibitors (ICIs) is not well known. Our objective was to determine the extent of, and identify gaps within, available literature addressing the effect of exercise on (a) oncological outcomes and (b) quality of life (QoL) in patients with cancer receiving ICIs, and (c) the underlying biological mechanisms for such effects. We conducted searches across EMBASE, APA PsycInfo and Ovid MEDLINE(R). Studies were eligible if they addressed at least one aspect of the objective and were available in the English language. Results were synthesised using a narrative approach and subsequently discussed with multidisciplinary stakeholders. As of the final search on 5 April 2022, 11 eligible studies were identified, of which 8 were preclinical and 3 were clinical. Clinical studies only focused on QoL-related outcomes. When studies were grouped by whether they addressed oncological outcomes (n = 7), QoL (n = 5) or biological mechanisms (n = 7), they were found to be heterogeneous in methodology and findings. Additional evidence, particularly in the clinical setting, is required before robust recommendations about whether, and how, to include exercise alongside ICI treatment can be made.

Introduction: For patients with cancer, immune checkpoint inhibitors (ICIs) produce superior long-term responses compared with alternative treatments, although at the cost of manifesting adverse immune-related events. There are many hypotheses of the impacts of physical activities in immunotherapy, but little is known about the oncological outcomes and the underlying mechanisms. This scoping review aims to identify possible physical activity interventions, their efficacy and feasibility and the potential underlying biological mechanisms responsible for their effects., Method and Analysis: The Levac methodology framework was used along with guidance from the Joanna Briggs Institute Manual for Evidence Synthesis to inform development of this protocol. Abstracts and titles followed by full-text screening will be performed by two independent reviewers for inclusion. All studies describing the impact of physical activities and exercise interventions on cancer ICIs, with particular focus on oncological outcomes, quality of life or underling biological mechanisms, will be included. After extracting qualitative and quantitative data, they will be evaluated and summarised, respectively. Subsequently, a further consultation step with other scientists and healthcare professionals will be performed., Ethics and Dissemination: The research findings will be published through an open-access peer-reviewed journal. The results of this scoping review will be used to inform further studies on physical impacts on immunotherapy. All data included will be from open resources, therefore, no ethical clearances are required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples ( n = 29). CTC count positively correlated with absolute total lymphocyte count (r 2 = 0.1709, p = 0.0258) and NK-cell count (r 2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r 2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group ( n = 123, p < 0.0001), the non-exercise group ( n = 79, p = 0.001) and blood draw samples lacking platelet cloaking ( n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group ( n = 15) had a higher proportion of CD3+ T-lymphocytes ( p = 0.0003) and lower proportions of B-lymphocytes ( p = 0.0264) and NK-cells ( p = 0.015) than the non-exercise group ( n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.

Introduction: Physical activity (PA) interventions have been introduced in patients with cancer as they may contribute to better treatment outcomes and quality of life (QoL). However, little is known about the impact of PA on patients with bladder cancer (BC). This scoping review aimed to explore efficacy and feasibility of existing PA interventions in the BC care pathway., Methods and Analysis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines and the Levac methodology framework were used; electronic databases were searched. Two independent reviewers screened all titles, abstracts and full-text publications for inclusion. The feasibility of integrating a PA intervention in the BC treatment pathway was discussed in a consultation phase with healthcare professionals and patient and public representatives., Results: A total of 675 records were identified through database searching of which 14 studies were included in our scoping review. An additional 17 clinical trials were identified of which 12 were included for which no results have been published yet. The included studies looked at the feasibility of a PA intervention programme, the associations between PA, obesity and BC, but also the determinants of PA engagement for BC patients and the assessment of QoL., Conclusion: This scoping review highlights that despite the general recognition on the role of PA in the BC treatment pathway, there is a gap regarding the understanding of the impact of PA interventions in BC care pathways as well as the limited understanding of factors underlying possible benefits of PA. No clear conclusions could be made regarding structure and processes of PA interventions that may lead to better outcomes. Further PA studies for patients with BC are needed to understand how to incorporate exercise guidelines recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bladder cancer (BC) is the 10 th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.

Purpose: Existing research indicates that physical activity (PA) is beneficial to men with prostate cancer (PCa). We examined the potential of a single-contact peer-support-based behavioural intervention to promote PA engagement in men treated for PCa., Methods: A mixed methods design was employed, comprising a two-arm pragmatic trial and semi-structured interviews. The intervention was a 10-min PA-based presentation by a former patient, delivered in group seminars that are provided for patients as standard care. Seminars were alternately allocated to (a) cancer exercise specialist talk + patient speaker talk or (b) cancer exercise specialist talk only. Self-reported PA, exercise motivation, quality of life, fatigue and clinical and demographic characteristics were obtained from n = 148 (intervention: n = 69; control: n = 79) patients immediately prior to the seminar, and at follow-up ≈ 100 days later. Data were analysed using ANCOVA models and χ 2 tests. Fourteen semi-structured interviews with intervention participants, which explored how the intervention was experienced, were analysed using a grounded theory-style approach., Results: The intervention had no significant effect on quantitatively self-reported PA (p = 0.4). However, the intervention was statistically and clinically beneficial for fatigue (p = 0.04) and quality of life (p = 0.01). Qualitative analysis showed that the intervention was beneficial to psychological wellbeing and some participants had increased intention to engage in PA as a result of the intervention., Conclusions: A brief one-off PA-based presentation for men with PCa, delivered by a former patient alongside cancer exercise specialist advice, may result in clinically significant benefits to quality of life and may influence PA intention in certain individuals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Objectives: The main objective of this study is to determine the feasibility of recruiting and retaining patients recently diagnosed with thoracic cancer to a trial of short-term integrated rehabilitation; evaluate uptake of theoretically informed components targeting physical function, symptom self-management and participation; estimate sample size requirements for an efficacy trial., Design: Parallel group randomized controlled feasibility trial., Setting: Three U.K. hospitals., Participants: Patients ⩽eight weeks of thoracic cancer diagnosis, Eastern Cooperative Oncology Group Performance Status 0-3, any cancer stage and treatment plan., Interventions: Participants randomly allocated (1:1) to short-term integrated rehabilitation and standard care or standard care alone over 30 days., Main Measures: Primary: participant recruitment and retention, targeting ⩾30% of eligible patients enrolling and ⩾50% of participants reporting outcomes at 30 days. Secondary: intervention fidelity; missing data and performance of outcome measures for self-efficacy, symptoms, physical activity and health-related quality of life., Results: Of 159 eligible patients approached, 54 (34%) were recruited. A total of 44 (82%) and 39 (72%) participants reported outcomes at 30 and 60 days, respectively. Intervention fidelity was high. Rehabilitation was delivered across 3 (1-3) sessions over 32 (22-45) days (median (range)). Changes in clinical outcomes were modest but most apparent at 60 days for health-related quality of life: Functional Assessment of Cancer Therapy Lung Cancer score median (interquartile range) change 9.7 (-12.0 to 16.0) rehabilitation versus 2.3 (-15.0 to 14.5) standard care., Conclusion: A trial to examine efficacy of short-term integrated rehabilitation for people newly diagnosed with thoracic cancer is feasible. A sample of 336 participants could detect a meaningful effect on health-related quality of life as the primary outcome.

Objective: Existing research indicates that moderate-to-vigorous physical activity (PA) alleviates treatment side effects and is associated with survival in men with prostate cancer. We aimed to ascertain the state of research investigating barriers and facilitators to PA in men with prostate cancer and synthesise existing qualitative research on this topic., Methods: A systematic review of qualitative and quantitative studies was conducted. MEDLINE, Embase, PsycINFO, Web of Knowledge, CINAHL, PEDro, OATD, and WorldCat were searched to June 2019 for quantitative studies investigating causes or predictors of PA or qualitative studies describing patient-reported barriers/facilitators to PA, amongst men with prostate cancer of any stage. Thirty-two studies (n = 17 quantitative; n = 15 qualitative) were included from 3698 screened articles., Results: Heterogeneity and unsystematic reporting of quantitative study methods prohibited a quantitative data synthesis. Thematic synthesis of qualitative studies produced five analytical themes: individual needs by treatment pathway, self-determination and its relationship with prostate cancer-related events, co-ordination and support of the clinical care team, individual preferences in discrete aspects of PA engagement style, and the potential for a bidirectional facilitative relationship between structured group PA and spontaneous peer support. Both qualitative and quantitative studies indicated incontinence as a barrier., Conclusions: Unsystematic reporting of interventions hinders a robust quantitative understanding of behavioural intervention research in this subject area. Good co-ordination of multidisciplinary care personnel could facilitate PA, by enabling a more comprehensive approach to targeting social cognitive processes. Well-timed intervention and access to highly individualised PA support, including optional group PA classes, seem to also be important facilitators., (© 2019 John Wiley & Sons, Ltd.)

Introduction: Patients with bladder cancer (BC) have been found to have worse experiences than those with other cancers which may partly be due to impact on quality of life. Currently, little is known about the impact of physical activity (PA) on BC outcomes. This scoping review aims to identify what interventions are available, their reported efficacy and feasibility, and a description of potential underlying biological mechanisms for their effects., Methods and Analysis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review (ScR) guidelines and the Levac methodology framework will be followed/used. Electronic databases will be searched (MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, OpenGray). Two independent reviewers will screen all abstracts and titles and during a second stage and full-text publications for inclusion. All studies describing PA (as an existing lifestyle or as part of an intervention programme) during BC management will be included. Study characteristics will be recorded; qualitative data will be extracted and evaluated using the Donabedian framework. Quantitative data will be extracted and summarised. A further consultation step will be carried out with patients, their family members and healthcare professionals., Ethics and Dissemination: Results will be disseminated through a peer-reviewed publication. Through the consultation step, we will ensure that findings will reach a wide audience and recommendations can be made for future development of PA interventions for patients with BC. Data used will be from publicly available secondary sources, and the consultation step will be carried out as part of patient and public involvement so this study does not require ethical review., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Access to rehabilitation to prevent disability and optimise function is recommended for patients with cancer, including following cancer diagnosis. Models to integrate rehabilitation within oncology services as cancer treatment commences are required, but must be informed by those they are intended to support. We aimed to identify views of patients, carers and clinicians to develop and refine a rehabilitation model to be tested in a feasibility trial for people newly diagnosed with lung cancer or mesothelioma., Methods: We conducted a focus group study with people affected by lung cancer or mesothelioma, their carers and clinicians providing their care to identify priorities for rehabilitation in this period. We sought views on core intervention components, processes and outcomes and integration with oncology services. Data were analysed using thematic analysis., Results: Fifteen clinicians (oncologists, nurse specialists, physiotherapists and occupational therapists), nine patients and five carers participated. A proposed outline rehabilitation model was perceived as highly relevant for this population. Participants recommended prompt and brief rehabilitation input, delivered whilst people attend for hospital appointments or at home to maximise accessibility and acceptability. Participants recognised variation in need and all prioritised tailored support for symptom self-management, daily activities and the involvement of carers. Clinicians also prioritised achieving fitness for oncology treatment. Patients and carers prioritised a sensitive manner of approach, positivity and giving hope for the future. Participant's recommendations for outcome measurement related to confidence in usual daily activities, symptom control and oncology treatment completion rates over objective measures of cardiorespiratory fitness., Conclusion: The importance of providing tailored rehabilitation around the time of diagnosis for people with lung cancer or mesothelioma was affirmed by all participants. The refined model of rehabilitation recommended for testing in a feasibility trial is flexible, tailored and short-term. It aims to support people to self-manage symptoms, tolerate cancer treatments and to remain active and independent in daily life. It is delivered alongside scheduled hospital appointments or at home by an expert practitioner sensitive to the psycho-social sequelae that follow a diagnosis of thoracic cancer., Competing Interests: Ethical approval was received from the Health Research Authority London (Westminster Research Ethics Committee, reference: 16/LO/2035), and all participants provided written informed consent to participate.All participants provided written informed consent for publication of the findings, including anonymised quotes.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Metastatic disease is a frequent complication of advanced cancer, with bone representing one of the most common sites of metastatic occurrence. Patients with bone metastases receive long-term systemic treatments that have a significant attritional impact on muscle strength, fatigue, and physical functioning. Physical rehabilitation involving exercise and physical activity prescription has a considerable role in counteracting these changes; however, exercise is often perceived as a contraindication in the presence of bone metastases due to concerns about aggravating skeletal related events. This article examines the physical sequelae of bone metastases and outlines the factors for consideration with exercise prescription in metastatic bone disease, including bone health, pain levels, and oncologic treatment. This article includes a comprehensive review of the evidence from trials of exercise prescription in this population, including the efficacy and safety outcomes of exercise interventions. Exercise interventions for patients with bone metastases are associated with positive physical and self-reported outcomes. Studies reviewed reporting adverse events did not find a high fracture incidence with exercise in comparison with control participants, or an association between exercise and fracture risk. The need to individualize exercise prescription and adapt exercises to patient ability were reinforced in all papers reviewed. Exercise prescription to patients with bone metastases does involve complex decision making; however, a number of tools are available that may inform both the assessment of patients and the prescription of exercise., Level of Evidence: NA., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Background: Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer., Methods: This international multicentre prospective study will recruit men with metastatic prostate cancer. Participants will be recruited from centres in Dublin (Ireland) and London (UK). Participants will be divided into exposed and non-exposed groups based on body mass index (BMI) ≥ 25 kg/m 2 and randomised to intervention and control groups. The exercise group will undertake a regular supervised aerobic exercise programme, whereas the control group will not. Exercise intensity will be prescribed based on a target heart rate monitored by a polar heart rate monitor. Blood samples will be taken at recruitment and at 3 and 6 months to examine the primary endpoint of platelet cloaking of CTCs. Participants will complete a detailed questionnaire to assess quality of life (QoL) and other parameters at each visit., Discussion: The overall aim of the ExPeCT trial is to examine the relationship between PrCa, exercise, obesity, and systemic inflammation, and to improve the overall QoL in men with advanced disease. Results will inform future work in this area examining biological markers of prognosis in advanced prostate cancer., Trial Registration: Clinicaltrials.gov NLM identifier: NCT02453139 . Registered on 12 May 2015. This document contains excerpts from the ExPeCT trial protocol Version 1.5, 28 July 2016.

Pharmacokinetic interactions between chemotherapy and highly active antiretroviral therapy (HAART) are described, but there are few data on their clinical relevance. Patients with systemic AIDS-related non-Hodgkin lymphoma (ARL) were treated with concomitant HAART and infusional cyclophosphamide-doxorubicin-etoposide (CDE) chemotherapy. We compared neutropenia according to whether patients received protease inhibitor (PI)-based HAART or non-PI regimens. Differences in survival, response rates, immunologic parameters, and virologic parameters were also investigated. The day-10 (Mann-Whitney U test; P = .012) and day-14 (P = .025) neutrophil counts were significantly lower in patients receiving PIs, though there were no differences in the number of days of granulocyte colony-stimulating factor (G-CSF) administered between groups (P = .16). Grade 3 or 4 infections requiring hospitalization were recorded for a total of 58 (31%) of 190 cycles of CDE: 23 (48%) of 48 when prescribed PIs and 35 (25%) of 142 with concomitant PI-sparing HAART (chi(2) test; P = .0025). There were no statistically significant differences in the response rates, relapse-free survival, or disease-free survival between patients receiving PIs and those not receiving PIs. PI-based HAART appears to significantly potentiate the myelotoxicity of CDE chemotherapy. This potentiation may be a consequence of microsomal enzyme inhibition reducing the metabolism of cytotoxics in this regimen.

In the fission yeast Schizosaccharomyces pombe, transcriptional activation at Start is mediated by complexes that bind the MCB. Two such complexes have been identified; both contain the Cdc10 protein in partnership with either the Res1 or Res2 protein. Characterization of null mutants suggests that the Res1-Cdc10 complex predominantly functions in mitotic cells whereas the Res2-Cdc10 complex is required for meiosis and spore formation. Here we have characterized the functional domains of the Res2 protein. The N-terminus is both necessary and sufficient for DNA binding, whereas the C-terminus is the region involved in the interaction with the Cdc10 protein. The centrally located ankyrin repeats are dispensable for both functions. Res2 binds to DNA as a dimer. In addition, complexes containing both Res1 and Res2 can form and bind to DNA in vitro. Furthermore, the major MCB-specific complex detected in extracts from wild-type cells contains Res1 and Res2; the complex is lost when either gene is deleted and can be recognized by antibodies specific to both proteins. In order to understand the basis for the specific function of Res2 in meiosis, hybrids between Res1 and Res2 were constructed and their functions analysed. The results indicate an absolute requirement for the Res2 C-terminus for normal meiosis to occur whereas the origin of the DNA-binding region is irrelevant. The implications of these results for the regulation of the MCB-binding complexes will be discussed.

The human MUC1 gene codes for the core protein of a mucin which is expressed by glandular epithelia and the carcinomas which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucin, which also contains epitopes recognized by T-cells from breast and pancreatic cancer patients. For evaluating the potential use of mucin-reactive antibodies and mucin-based immunogens in cancer patients, a mouse model, expressing the MUC1 gene product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely useful. To this end, we have developed transgenic mouse strains expressing the human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was established using a 40-kilobase fragment containing 4.5 kilobases of 5' and 27 kilobases of 3' flanking sequence. The TG18 strain was developed using a 10.6-kilobase SacII fragment from the 40-kilobase fragment; this fragment contained 1.6 kilobases of 5' sequence and 1.9 kilobases of 3' flanking sequence. Both strains showed tissue specificity of expression of the MUC1 gene, which was very similar to the profile of expression seen in human tissues. The antibody SM-3 is directed to a core protein epitope, which is selectively exposed in breast cancers and which shows a more restricted distribution on normal human tissues. It was established that the distribution of the SM-3 epitope of PEM in the tissues of the transgenic mice is similar to that seen in humans. The transgenic mouse strains described here should form the basis for the development of a preclinical model for the evaluation of PEM-based antigens and of antibodies directed to PEM in cancer therapy.