34 research outputs found

    TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

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    TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis

    Testing the leadership and organizational change for implementation (LOCI) intervention in substance abuse treatment: A cluster randomized trial study protocol

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    © 2017 The Author(s). Background: Evidence-based practice (EBP) implementation represents a strategic change in organizations that requires effective leadership and alignment of leadership and organizational support across organizational levels. As such, there is a need for combining leadership development with organizational strategies to support organizational climate conducive to EBP implementation. The leadership and organizational change for implementation (LOCI) intervention includes leadership training for workgroup leaders, ongoing implementation leadership coaching, 360° assessment, and strategic planning with top and middle management regarding how they can support workgroup leaders in developing a positive EBP implementation climate. Methods: This test of the LOCI intervention will take place in conjunction with the implementation of motivational interviewing (MI) in 60 substance use disorder treatment programs in California, USA. Participants will include agency executives, 60 program leaders, and approximately 360 treatment staff. LOCI will be tested using a multiple cohort, cluster randomized trial that randomizes workgroups (i.e., programs) within agency to either LOCI or a webinar leadership training control condition in three consecutive cohorts. The LOCI intervention is 12months, and the webinar control intervention takes place in months 1, 5, and 8, for each cohort. Web-based surveys of staff and supervisors will be used to collect data on leadership, implementation climate, provider attitudes, and citizenship. Audio recordings of counseling sessions will be coded for MI fidelity. The unit of analysis will be the workgroup, randomized by site within agency and with care taken that co-located workgroups are assigned to the same condition to avoid contamination. Hierarchical linear modeling (HLM) will be used to analyze the data to account for the nested data structure. Discussion: LOCI has been developed to be a feasible and effective approach for organizations to create a positive climate and fertile context for EBP implementation. The approach seeks to cultivate and sustain both effective general and implementation leadership as well as organizational strategies and support that will remain after the study has ended. Development of a positive implementation climate for MI should result in more positive service provider attitudes and behaviors related to the use of MI and, ultimately, higher fidelity in the use of MI. Trial registration: This study is registered with Clinicaltrials.gov ( NCT03042832 ), 2 February 2017, retrospectively registered

    Lumbar Facet Joint Orientation in Degenerative Spondylolisthesis: the Role of Ethnic Variation in Asia Pacific

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    General PosterINTRODUCTION: Lumbar facet joint orien‐ tation has been reported to be associated with the development of degenerative spondylolisthesis (dSpl). The role of ethnici‐ ty regarding facet joint orientation remains uncertain. As such, the following study was performed across a wide‐ranging popula‐ tion base to assess the role of ethnicity in facet joint orientation in patients with dSpl in the Asia Pacific region. METHODS: A multi‐national, multi‐ethnic cross‐sectional image‐based study was per‐ formed in 34 institutions in Asia Pacific, identifying 448 cases. Lateral standing x‐ rays and axial MRIs and/or CT scans were obtained for patients with lumbar dSpl. Magnitude of slip displacement, level of dSpl, and left/right facet joint angulation, width‐curvature ratio, and gap width were noted on image assessment. Facet joint measurements were performed at each level from L3‐S1. Gender, age, BMI, and ethnicity were also noted.    RESULTS: The study included 389 patients with known ethnic origin (mean age: 61.4 years; 36.7% males, 63.3% females). The mean BMI was 25.6 kg/m2. The level of dSpl was most prevalent at L4/L5 (72.4%). There were 28.8% Indian, 28.5% Japanese, 17.5% Chinese, 8.2% Korean, 6.2% Thai, 4.6% Cau‐ casian, 2.3% Filipino, 2.3% Malay, and 1.3 were of mixed Asian origin. Accounting for patient demographics and displacement, there was a statistically significant differ‐ ence between ethnicity to that of left/right facet joint angulations, width‐curvature ratios, and gap widths from L3‐S1 between specific ethnic groups (p<0.05).    DISCUSSION: This is the largest study to address the role of ethnicity upon lumbar facet joint orientation in dSpl. Ethnicity plays a role in facet joint orientation and may influence the occurrence and severity of dSpl or be a potential consequence. An understanding of ethnic variability may be one factor which assists in identifying those patients at risk of postsurgical development or progression of dSpl

    Is lumbar facet joint tropism developmental or secondary to remodeling changes? An international, large-scale multicenter study by the AOSAP collaboration consortium

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    Session: Free Papers Spine: Degenerative 1: abstract no. 40328INTRODUCTION: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether FJT is a pre-existing developmental phenomena or secondary to progressive joint remodeling. The following study addressed the occurrence of FJT of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. METHODS: This was an international, multi-center cross-sectional study of 267 patients with single level DS recruited from 33 spine institutes in Asia Pacific. FJT (≥8 degrees asymmetry) was assessed on MRI from L3-S1 and in relation to the level of DS. Patient demographic were noted and assessed in relation to FJT of each lumbar segment. RESULTS: 65% were females (mean age of 63 years; mean BMI: 26 kg/m2). FJT was present in 31.3% to 50.6% of DS levels. FJT involved 33.3% to 58.8% of the one or two non-DS levels adjacent to the DS level. Patient demographics were not found to be significantly related to FJT at any level (p>0.05). CONCLUSION: To the authors’ knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing the “origins concept” of FJT. Although levels with DS were noted to have FJT, adjacent levels with no DS also exhibited tropism and were not related to age and other patient demographics. This study suggested that FJT may have a pre-disposed orientation

    Is lumbar facet joint tropism development or secondary to remodeling changes? An international, large-scale multi-centre study by the APSAP collaboration consortium

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    Session - Free Papers Spine Degenerative 1: abstract no. 40328INTRODUCTION: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether FJT is a pre-existing developmental phenomena or secondary to progressive joint remodeling. The following study addressed the occurrence of FJT of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. METHODS: This was an international, multi-center cross-sectional study of 267 patients with single level DS recruited from 33 spine institutes in Asia Pacific. FJT (≥8 degrees asymmetry) was assessed on MRI from L3-S1 and in relation to the level of DS. Patient demographic were noted and assessed in relation to FJT of each lumbar segment. RESULTS: 65% were females (mean age of 63 years; mean BMI: 26 kg/m2). FJT was present in 31.3% to 50.6% of DS levels. FJT involved 33.3% to 58.8% of the one or two non-DS levels adjacent to the DS level. Patient demographics were not found to be significantly related to FJT at any level (p>0.05). CONCLUSION: To the authors’ knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing the “origins concept” of FJT. Although levels with DS were noted to have FJT, adjacent levels with no DS also exhibited tropism and were not related to age and other patient demographics. This study suggested that FJT may have a pre-disposed orientation
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