scholarly journals Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome

Oncotarget ◽  
2016 ◽  
Vol 7 (10) ◽  
pp. 11165-11193 ◽  
Author(s):  
Linlin Luo ◽  
Peter McGarvey ◽  
Subha Madhavan ◽  
Rakesh Kumar ◽  
Yuriy Gusev ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Family Members ◽  
Lymphocyte Antigens

scholarly journals Pre-Clinical Investigation of Targeted Therapies for Double Hit Diffuse Large B-Cell Lymphoma (DH-DLBCL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5122-5122
Author(s):  
Priyank P. Patel ◽  
Alison Zeccola ◽  
Vishala T. Neppalli ◽  
Juan J Gu ◽  
Cory Mavis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Clinical Outcome ◽  
B Cell ◽  
Cell Lines ◽  
Family Members ◽  
Lymphoma Cell ◽  
Gene Rearrangements ◽  
Synergistic Activity ◽  
Poor Clinical Outcome

Abstract Background: Molecular studies divide DLBCL into three subtypes with distinct pathogenesis and clinical outcomes: activated B-cell (ABC), germinal center B-cell (GCB) and primary mediastinal lymphoma (PML). Florescence in situ hybridization (FISH) studies identified another subgroup of DLBCL, classified as DH-DLBCL, with a poor clinical outcome harboring concurrent gene rearrangements of the c-MYC, BCL2 and/or BCL6 proto-oncogenes, resulting in the over-expression of c-Myc, Bcl2 and Bcl6 proteins. DH-DLBCL has inferior response rates (RR) to rituximab-based chemotherapy, and a shorter progression-free survival (PFS)/overall survival (OS). DH-DLBCL is characterized by de-regulation of apoptosis and cell cycle progression, resulting in rapid cellular proliferation and resistance to apoptotic stimuli. In ABC-DLBCL, anti-apoptotic factor MCL-1 is implicated in poor prognosis leading to resistance to standard chemotherapy. C-MYC transcriptionally upregulates Mcl1. Translocation of c-MYC in DH-DLBCL may contribute to the aggressive phenotype and chemotherapy resistance via the MCL-1 pathway. We hypothesize that dual inhibition of both anti-apoptotic proteins BCL2 and MCL1 is an effective strategy in inducing lymphoma cell death in DH-DLBCL. Materials & Methods: At the pre-clinical level, we studied novel therapeutic strategies targeting key-regulatory pathways abnormally enhanced by the dual BCL2/BCL6 and c-MYC gene rearrangements or amplification using DH lymphoma cell lines (Val, DOHH-2, ROS-50). We evaluated the therapeutic value of three novel agents targeting BCL2 (ABT199), c-MYC (JQ-1), and cell cycle regulatory proteins (p21) and other BCL2 family members affecting ABT199 activity (carfilzomib (CFZ), an irreversible proteasome inhibitor) in a panel of DH-DLBCL cell lines. We retrospectively evaluated our single institution outcome experience over the last 15 years in DH-DLBCL patients. Using the lymphoma translational database that includes 611 DLBCL patients, we identified 30 patients (M=17/F=13) with aberrations in c-MYC and BCL2 or BCL6 by FISH. Demographic characteristics and clinical data were collected and analyzed. Results: In vitro, ABT199, JQ-1, and CFZ induced cell death in a dose- and time-dependent manner. Significant synergistic activity was observed by combining ABT199 with CFZ and to a lesser degree with JQ-1. Subsequently, we studied the outcome of DHL patients treated at our institute. Mean age at diagnosis was 63 years, mostly Caucasians (N=28). Using the Han's algorithm, 21 of the DH-DLBCL were GCB, 8 were non-GCB, and 1 unclassifiable. 22 patients had rearrangement of c-MYC and BCL2/ or BCL-6 by FISH and 8 had gain/amplification/aneuploidy at these loci. At diagnosis, 96% (n=29) patients presented with stage III/IV, 67% (n=20) with High-intermediate/High IPI score, and 77% (n=23) had extra nodal disease. Front-line chemo-immunotherapy included 1) standard doxorubicin-containing regimens: R-CHOP (N=11) or R-EPOCH (N=8), or 2) intensified regimens: R-DHAC (N=3) and R+HyperCVAD/R+HDMTXCytarabine (N=8). Prophylaxis IT chemotherapy was administered to 21 (70%) patients. The complete remission (CR) rate was 67% (n=20) and 37% (n=11) patients underwent HDC-ASCS (N=9)/allo-BMT (N=2) in first (N=9) or second-remission (N=2). The use of intensified regimens was associated with a non-statistically significant improvement is PFS and OS. Similarly, an improvement in OS was observed among patients receiving HDC-ASCT/allo-BMT as consolidation. As previously noted, CNS prophylaxis was associated with an improvement in OS. Mcl-1 and other Bcl-2 family members expression levels are been determined by IHC. These results highlight the poor clinical outcome of this patient population and the need for alternative therapeutic options. Conclusion: Our data suggests that ABT199 exhibited strong synergistic activity with CFZ. Dual targeting of BCL2 and c-MYC pathways results in synergistic activity in DHL cell lines. Of interest, this pharmacological interaction could be related to the effects of proteasome inhibition on MCL1 and p21 levels in lymphoma cells, further enhancing the activity of ABT199. Using combination therapy to inhibit c-MYC and the proteasome and in turn decreasing MCL1 will render ABT-199 more effective and be a more potent combination in causing apoptosis and lymphoma cell death. Further pre-clinical work is ongoing. Disclosures No relevant conflicts of interest to declare.

O18 Activated leukocyte cell adhesion molecule (ALCAM) and its intracellular linkers in assessing the outcome of patients with breast cancer

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
Y M Yang ◽  
A J Sanders ◽  
E Davies ◽  
R E Mansel ◽  
W G Jiang
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Prognostic Factor ◽  
Clinical Outcome ◽  
Prognostic Value ◽  
Family Members ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Good Prognosis ◽  
Significant Prognostic Factor

Abstract Introduction ALCAM (also known as CD166) is a membrane integral protein and said to have a role in predicting the clinical outcome of patients with breast cancer, but the pattern of the prediction value is inconsistent. ALCAM confers cell-cell adhesion via heterotypic and homotypic interactions and linked to cytoskeleton via the ERM protein family (Ezrin, Moesin, Radixin and EHM2), particularly ezrin. The present study explored if the ALCAM and its ERM linkers may assist in refining the prognostic value of ALCAM. Method Gene transcripts of ACLAM and the ERM family members were quantitatively analysed in an existing breast cancer cohort collected freshly after surgery. The relationship between ALCAM and patient’s survival (follow-up 10 years) were stratified by the ALCAM linkers. Statistical methods were Kaplan-Meier’s survival method, ROC and logistic regression. Result ALCAM significantly correlated with four ERM family members (P < 0.005). Patients with high levels of ALCAM transcripts had significantly long overall survival. Further stratification by the epithelial rich Ezrin and endothelial rich Moesin identified subgroup of patients with good prognosis. Multivariant analysis indicates that the combined power of ALCAM and ERM family serves as an independent prognostic factor (P = 0.003) together with the other two factors, namely the Nottingham Prognostic Index and Nodal status (P = 0.02). A similar prediction power for disease free survival was seen with ALCAM and ERM combination. Conclusion ALCAM and its intracellular cytoskeletal linker molecules, the ERM family, together forms a significant prognostic factor to the clinical outcome of patients with breast cancer. Take-home Message ALCAM stratified by the ERM family have prognostic value in breast cancer

The 15-item Systemic Clinical Outcome and Routine Evaluation (SCORE-15) Scale: Portuguese Validation Studies

2015 ◽  
Vol 18 ◽  
Author(s):  
Margarida Vilaça ◽  
Bruno de Sousa ◽  
Peter Stratton ◽  
Ana Paula Relvas
Keyword(s):  
Clinical Outcome ◽  
Family Functioning ◽  
Predictive Validity ◽  
Family Communication ◽  
Convergent Validity ◽  
Discriminant Validity ◽  
Family Members ◽  
Clinical Samples ◽  
Family Strengths ◽  
Evaluation Score

AbstractThis study reports on the validity of the 15-item Portuguese version of the Systemic Clinical Outcome Routine Evaluation (SCORE-15; Vilaça, Silva, & Relvas, 2014), a brief and comprehensive measure of family functioning. Previous studies with SCORE-15 show that this version replicates the three-factor solution found for the original English version: Family strengths, Family communication and Family difficulties. In addition to reviewing previous studies, this article analyses the discriminant, convergent and predictive validity of the Portuguese SCORE-15. To do so, the SCORE-15 was administered to family members attending systemic family or couple’s therapy at the start of the first and fourth sessions and also to a group of non-clinical individuals. Overall, data are reported from 618 participants, including 136 from families attending systemic therapy and 482 community family members. Comparisons of community and clinical samples (discriminant validity) showed statistically significant differences for the total scale and subscales (p < .001), with the community participants presenting healthier family functioning than the clinical ones. Analyses using SCORE-15 and the Quality of Life – adult version, another family measure applied simultaneously (convergent validity), indicate that both scales are significantly (p < .01) and moderately (r = –.47) correlated. Mean score analysis of SCORE-15’s therapeutic sensitivity to change (predictive validity) showed that only the Family communication subscale was sensitive to statistically significant improvement (p < .05) from session 1 to session 4, whereas the SCORE-15’s reliability change index points to its ability to detect clinical improvements (RCI = 14%).

scholarly journals Collaboration between Social Workers and Families of Patients with Mental Illness

1993 ◽  
Vol 74 (2) ◽  
pp. 104-115 ◽  
Author(s):  
Neal DeChillo
Keyword(s):  
Mental Illness ◽  
Social Work ◽  
Clinical Outcome ◽  
Severe Mental Illness ◽  
Social Workers ◽  
Family Involvement ◽  
Discharge Planning ◽  
Family Members ◽  
Inpatient Unit ◽  
High Degree

The author examines collaboration between families of patients with severe mental illness and inpatient social workers as measured by a study that assessed the degree to which families and practitioners collaborate, factors that influence collaboration, and the effects of collaboration on clinical outcome. Social workers and family members were surveyed at the time of the patient's discharge from the inpatient unit. Findings revealed a relatively high degree of collaboration. The strongest predictor of collaboration was the practitioner's attitude toward family involvement in the patient's treatment. In addition, higher levels of collaboration were significantly correlated with increased family involvement in discharge planning and satisfaction with social work services.

scholarly journals Feasibility of Group Problem Management Plus (PM+) to improve mental health and functioning of adults in earthquake-affected communities in Nepal

2020 ◽  
Vol 29 ◽  
Author(s):  
M. Sangraula ◽  
E. L. Turner ◽  
N. P. Luitel ◽  
E. van ‘t Hof ◽  
P. Shrestha ◽  
...  
Keyword(s):  
Mental Health ◽  
Randomised Controlled Trial ◽  
Clinical Outcome ◽  
Health Workers ◽  
Controlled Trial ◽  
Family Members ◽  
Depression Symptoms ◽  
Problem Management ◽  
Randomised Controlled ◽  
Programme Staff

Abstract Aims Psychological interventions that are brief, acceptable, effective and can be delivered by non-specialists are especially necessary in low- and middle-income countries, where mental health systems are unable to address the high level of psychosocial needs. Problem Management Plus (PM+) is a five-session intervention designed for those impaired by psychological distress while living in communities affected by adversity. Individual PM+ has demonstrated effectiveness in reducing distress in Kenya and Pakistan, and a group version of PM+ (Group PM+) was effective for conflict-affected women in Pakistan. This paper describes a feasibility and acceptability trial of locally adapted Group PM+ for women and men in an earthquake-affected region of rural Nepal. Methods In this feasibility cluster randomised controlled trial, participants in the experimental arm were offered five sessions of Group PM+ and participants in the control arm received enhanced usual care (EUC), which entailed brief psycho-education and providing referral options to primary care services with health workers trained in the mental health Gap Action Programme Intervention Guide (mhGAP-IG). A mixed-methods design was used to assess the feasibility and acceptability of Group PM+. Feasibility was assessed with criteria including fidelity and retention of participants. Acceptability was assessed through in-depth interviews with participants, family members, programme staff and other stakeholders. The primary clinical outcome was depression symptoms assessed using the Patient Health Questionnaire (PHQ-9) administered at baseline and 8–8.5 weeks post-baseline (i.e. after completion of Group PM+ or EUC). Results We recruited 121 participants (83% women and 17% men), with equal allocation to the Group PM+ and EUC arms (1:1). Group PM+ was delivered over five 2.5–3 hour sessions by trained and supervised gender-matched local non-specialists, with an average attendance of four out of five sessions. The quantitative and qualitative results demonstrated feasibility and acceptability for non-specialists to deliver Group PM+. Though the study was not powered to assess for effectiveness, for all five key outcome measures, including the primary clinical outcome, the estimated mean improvement was larger in the Group PM+ arm than the EUC arm. Conclusion The intervention and trial procedures were acceptable to participants, family members, and programme staff. The communities and participants found the intervention to be beneficial. Because feasibility and acceptability were established in this trial, a fully powered randomised controlled trial will be conducted for larger scale implementation to determine the effectiveness of the intervention in Nepal.

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