Search

Overlapped genes between Genes upregulated in Ptenpc-/-Smad4pc-/- tumors as compared to Ptenpc-/- tumors ({greater than or equal to}2 fold) and genes upregulated in GFP+ tumors cells from Ptenpc-/-Smad4pc-/- mice as compared to Tomato+ cells ({greater than or equal to}4 fold).

Supplementary Figure S1. CyTOF analysis of biological samples from Ptenpc-/-Smad4pc-/- mice (Related to Figure 2). Supplementary Figure S2. Strategy used for MDSCs Isolation (Related to Figure 3). Supplementary Figure S3. Treatment scheme for Gr-1 antibody, peptibody, and Cxcr2 inhibitor SB225002. Supplementary Figure S4. IHC staining of Ki67, CD45, Vimentin, Smooth muscle actin (SMA) and Trichrome staining of mouse prostate tissues treated with IgG control or Gr1 antibody. Supplementary Figure S5. The top 10 differentially expressed genes in Ptenpc-/-Smad4pc-/- tumors as compared to Ptenpc-/- tumors, identified by microarray analysis (n=5). Figure S6. Top 10 activated oncogenic signatures identified by GSEA analysis in Ptenpc-/- Smad4pc-/- tumors as compared to Ptenpc-/- tumors (n=5). Figure S7. Clustering of primary prostate tumors from Wallace et al into MDSC-high and MDSC-low subtypes.

The Broad Cancer Cell Line Factory (CCLF) aims to increase the number and representation of in vitro/ex vivo cell models for common and rare cancer types. Neuroendocrine tumor (NET) cell model derivation is one of the CCLFs focus because it lacks well-characterized, publicly available models.Two major barriers existed in deriving NET cell models, including how to collect sufficient patient tumor tissue samples for the model derivation pilot and how to systematically iterate model derivation strategies since there is no prior knowledge for NET cell model generation success. Thus, we partnered with the MD Anderson Cancer Center, the Dana-Farber Cancer Institute, and the Rare Cancer Research Foundation to collect patient tissue samples. All patient’s NET tissues were sequenced with a targeted Pan-Cancer panel to ensure high tumor content. To reduce fibroblast outgrowth, we combined an empirical rich media matrix (HYBRID technology) with a 3D spheroid culture system to initiate one sample in 16-64 conditions. The growing cultures at passage 3-5 were genomically credentialed to ensure the driver events matched with the original patient tissue. So far, we have received more than 70 NET samples. While several derived models are still under culture, we successfully generated 5 genomically verified NET tumor models, including small intestinal, pancreas, and liver subtypes. To phenotypically characterize these NET models, neuroendocrine biomarkers such as chromogranin A, synaptophysin, SSTR2, and VMAT 1/2 were also evaluated using qRT-PCR and ELISA. We observed that these NET spheroid models display long doubling times (2-4 weeks) at later passages which limits their utility for large scale perturbation experiments and model sharing capability with the research community. While we are currently working on several strategies to improve the propagation ability in these models, 1 (out of 5) model has reached passage 15 with a 3 day doubling time. Genomic studies, such as RNAseq, will be performed to address the model transcriptome changes after overcoming growth plateaus. Here we showed that it is feasible to derive NET models from patient biospecimens using our HYBRID strategy. As we expand our NET cohort, we will further refine disease-specific model generation protocols for different NET types. Our goal is to share our model generation experience and make these tumor cell models publicly available to the research community in order to accelerate cancer research. Citation Format: Adel Attari, Madison Liistro, Barbara Van Hare, Jennifer Chan, Emma Coleman, Tim Heffernan, Bianca Amador, Matthew Meyerson, Jesse Boehm, William Sellers, Yuen-Yi (Moony) Tseng. A systemic model derivation platform for generating 3D neuroendocrine tumor cell spheroids to accelerate cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 197.

Background Consumer peer workers are individuals with lived experience of mental health issues and recovery who are employed to use their lived experience to support others. The consumer peer workforce has expanded substantially in recent years. While some research has explored the workplace experiences of peer workers, no previous studies have explored job satisfaction, burnout or turnover intention for this workforce. Methods Consumer peer workers in New South Wales, Australia were invited to complete a survey designed to explore their workplace experiences. The survey included measures of job satisfaction, burnout, turnover intention, job demands and job resources, and satisfaction with supervision, professional development and opportunities for career progression. Questions also explored positive and negative aspects of positions. Analyses included exploration of the relationships between of job satisfaction, burnout, turnover intention, job demands and job resources as well as tabulation of common positive and negative aspects of positions. Results were also compared with findings from a previous study exploring workplace experiences of other mental health workers. Results A total of 67 peer workers participated in the study. Overall job satisfaction, burnout (disengagement and exhaustion) and turnover intention for peer workers was not significantly different to other mental health workers. Job satisfaction, disengagement, exhaustion and turnover intention were all significantly inter-related. Job resources of social support, job control, feedback, and rewards and recognition were associated with positive workplace experiences and the job demand of “physical environment” was most substantially associated with poorer workplace experiences. The most common positive aspect of positions was “connecting with consumers” and the most common negative aspect of positions was “attitudes of clinicians / workplace culture”. Access to supervision from a senior peer worker was associated with more positive workplace experiences. Conclusions This research demonstrates that while consumer peer workers do not appear to experience poorer job satisfaction or higher levels of burnout or turnover intention than other mental health workers, a range of challenges do exist. Efforts to further expand the peer workforce (especially senior peer worker roles) and to promote more positive attitudes and workplace cultures are likely to promote better workplace experiences for peer workers.

Background Mental health recovery is still largely clinically defined and as such can lack person centeredness. To address this, recovery oriented experiences are required which recognise the holistic and diverse needs of individuals. Aim The aim of the study was to examine the experiences of people living with a mental illness who participated in a recovery oriented program called Recovery Camp. The study aimed to examine how the program may have related and contributed to their mental health recovery. Methods A descriptive phenomenological approach guided the study. Consenting participants ( n =5) were interviewed and asked about their subjective experience of Recovery Camp . The interviews were digitally audio recorded and transcribed verbatim. Data were analysed using van Kaam's Psychophenomenological method. Findings This paper presents the perspective of consumers regarding the ways in which Recovery Camp facilitated mental health recovery. Data analysis revealed five themes (Self-determination, Participation, Extending Self, Relationships and Positive change) and a core essence of meaning (Empowerment). Conclusions Personal mental health recovery for people living with mental illness can be enhanced through recovery oriented mental health care approaches. Findings contribute to existing literature regarding therapeutic recreation and its link to mental health recovery.

People living with mental illness (consumers) often experience difficulty in achieving life goals, particularly those important for their recovery. An innovative approach to address consumers' goals for recovery can be found in the form of therapeutic recreation (TR) initiatives. Recovery Camp is a five-day TR program, bringing together people with a serious mental illness, undergraduate health students, and staff members. This article aims to examine the types of goals set by consumers in the context of Recovery Camp, and to what extent the self-identified goals were attained. The consumers (n = 27) were invited to set goals that they wished to achieve during the week. On the final day of Recovery Camp, each participant rated the degree to which they felt that each of their goals was achieved or not. The goals were themed using content analysis, revealing four key themes: connectedness, developing healthy habits, challenging oneself, and recovery. All goals were, to some extent, attained. The results suggest people with a mental illness are able to both set and evaluate the self-identified goals in the context of a TR initiative. A collaborative recovery approach indicates that goal planning should be undertaken in direct consultation with the consumer.

Introduction There exists a need for innovative thinking to identify new clinical placement opportunities for nursing students. Recovery-based clinical placements for mental health nurse students remain unique and require investigation. Aim To examine the learning experience of Bachelor of Nursing students who undertook an innovative mental health clinical placement known as Recovery Camp . Design This study incorporated qualitative analysis of written reflections. Using Braun and Clarke's (2006) six phases of thematic analysis the corpus of student reflections were reviewed by three members of the research team independent to each other. Findings Four themes emerged. The theme of Pre-placement Expectations incorporates participant foci on pre-conceptions of Recovery Camp . The theme of Student Learning incorporates the ways in which participants recognised the experience of Recovery Camp influenced learning. Reflections themed under the title Placement Setting include discussion of the Recovery Camp as a clinical placement. The theme of Future Practice incorporates students' reflections on how they plan to practice as nurses as a result the learning experiences of Recovery Camp . Conclusions An immersive clinical placement such as Recovery Camp can influence students' perceptions of people with mental illness, have a positive impact on student learning and influence students' decisions about future practice. The learning experience of nursing students whom attend unique, recovery-orientated clinical placements can be both positive and educative.

Background The way people who experience mental illness are perceived by health care professionals, which often includes stigmatising attitudes, can have a significant impact on treatment outcomes and on their quality of life. Objective To determine whether stigma towards people with mental illness varied for undergraduate nursing students who attended a non-traditional clinical placement called Recovery Camp compared to students who attended a ‘typical' mental health clinical placement. Design Quasi-experimental. Participants Seventy-nine third-year nursing students were surveyed; n =40 attended Recovery Camp (intervention), n =39 (comparison group) attended a ‘typical' mental health clinical placement. Methods All students completed the Social Distance Scale (SDS) pre- and post-placement and at three-month follow-up. Data analysis consisted of a one-way repeated measures analysis of variance (ANOVA) exploring parameter estimates between group scores across three time points. Two secondary repeated measures ANOVAs were performed to demonstrate the differences in SDS scores for each group across time. Pairwise comparisons demonstrated the differences between time intervals. Results A statistically significant difference in ratings of stigma between the intervention group and the comparison group existed. Parameter estimates revealed that stigma ratings for the intervention group were significantly reduced post-placement and remained consistently low at three-month follow-up. There was no significant difference in ratings of stigma for the comparison group over time. Conclusions Students who attended Recovery Camp reported significant decreases in stigma towards people with a mental illness over time, compared to the typical placement group. Findings suggest that a therapeutic recreation based clinical placement was more successful in reducing stigma regarding mental illness in undergraduate nursing students compared to those who attended typical mental health clinical placements.

TransPoC is a not-for-profit research organization that will deliver open-access, large-scale translational oncology platforms to enable greater clinical proof-of-concept success for new cancer therapies. TransPoC will comprise three platforms: 1. CPN - Cancer Cell “PoC” Network for screening compounds against 1000+ genomically-characterized cell lines; 2. MPN- Mouse “PoC” Network - a multi-site platform for mouse preclinical trials using genomically-characterized Patient-Derived Xenograft (PDX) models; 3. BioIT - analysis and integration of genomic information and pharmacological profiling data. Here we present an overview of the Mouse “PoC” Network, define a path to implementation of multi-center pre-clinical trials in mice and describe a pilot study to demonstrate the feasibility of implementing such a network. PDX models are increasingly used in pre-clinical studies as they capture and retain the histological, molecular, and genetic heterogeneity of the original tumor compared to cell line derived xenografts and are therefore a closer representation of a patient's tumor in situ. To enable transformative preclinical studies, models need to be characterized in a manner similar to tumor samples in The Cancer Genome Atlas and the International Cancer Genome Consortium, and must be assembled in sufficient quantity to capture clinically relevant major cancer (sub)types. To achieve this, TransPoC is building a global network of mouse PDX “hospitals” with genomic and metabolomic profiles characterized in a consistent manner. In addition, each mouse hospital will utilize common SOPs to generate comparable pharmacology data sets across sites that will include testing standard of care agents. BioIT will enable deep interrogation of data sets and provide pipelines for pharmacogenomics correlates of response to both standard and novel agents. To date, the network has collated over 2,000 PDX models and will enable sponsors to execute multi-center pre-clinical trials in a manner similar to those used in multi-institutional cooperative clinical trials. To demonstrate the viability of MPN, a pilot study has been initiated at 6 sites located in Canada, Italy, China and USA to evaluate the activity of MEK and RAF inhibitors against a panel of BRAF/KRAS mutant melanoma and colorectal cancer PDX models. An update on the initial tolerability, PK/PD/efficacy studies and molecular characterization of PDX models in the network will be presented. TransPoC continues to recruit new sites and characterize their PDX models for incorporation into MPN for use by TransPoC sponsors. Through this effort TransPoC enables rapid assessment of standard and novel investigational therapies to determine their therapeutic potential for translation to clinical trials with a mission to improve the chance of observing clinical proof-of-concept. Citation Format: Peter G. Smith, David Sutton, Andrea Bertotti, Livio Trusolino, Susan Airhart, Ming S. Tsao, Bradly G. Wouters, S. Gail Eckhardt, Lai Wang, Tim Heffernan, David Verbel, Andrea Gerken, Peter Fekkes, Lihua Yu, Lihua Yu, Markus Warmuth. Translational Proof-of-Concept (TransPoC), a not-for-profit research organization enabling access to large-scale translational oncology platforms: The Patient-Derived Xenograft network. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1191. doi:10.1158/1538-7445.AM2014-1191