Head and Neck Diseases by Alexandros G.Sfakianakis

Τετάρτη 6 Ιανουαρίου 2016

nMET, a new target in recurrent cancer.

nMET, a new target in recurrent cancer.

Curr Cancer Drug Targets. 2016 Jan 4;

Authors: Xie Y, Istayeva S, Chen Z, Tokay T, Zhumadilov Z, Wu D, Hortelano G, Zhang J

Abstract
Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but ligand-dependent (full length Met) and -independent (cleaved Met) manner. nMET may play greater essential roles in cancer recurrence than membranous Met. For example in prostate cancer, it has been found that androgen receptor (AR) may inhibit the expression of membranous Met so anti-androgen based prostate cancer therapy may promote the expression of nuclear Met (nMET). We recently found a novel nMET/SOX9/β-Catenin/AR pathway in relapsed prostate cancer which may contribute to the formation of the feedback loop of AR reactivation via MET/nMET. Emerging evidence suggests the possibility of nMET as a prognostic marker in relapsed cancer. This review summarizes recent findings about nMET and its unique role in recurrent cancer.

PMID: 26728040 [PubMed – as supplied by publisher]

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Immune-related adverse events with immune checkpoint blockade: a comprehensive review

Publication date: February 2016
Source:European Journal of Cancer, Volume 54
Author(s): J.M. Michot, C. Bigenwald, S. Champiat, M. Collins, F. Carbonnel, S. Postel-Vinay, A. Berdelou, A. Varga, R. Bahleda, A. Hollebecque, C. Massard, A. Fuerea, V. Ribrag, A. Gazzah, J.P. Armand, N. Amellal, E. Angevin, N. Noel, C. Boutros, C. Mateus, C. Robert, J.C. Soria, A. Marabelle, O. Lambotte
Cancer immunotherapy is coming of age; it has prompted a paradigm shift in oncology, in which therapeutic agents are used to target immune cells rather than cancer cells. The first generation of new immunotherapies corresponds to antagonistic antibodies that block specific immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. Targeting these checkpoints in patients living with cancer had led to long-lasting tumour responses. By unbalancing the immune system, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (IRAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung but can potentially affect any tissue. In view of their undisputed clinical efficacy, anti-CTLA-4 and anti-PD-1 antibodies are entering in the routine oncological practice, and the number of patients exposed to these drugs will increase dramatically in the near future. Although steroids can be used to treat these IRAEs, the associated immunosuppression may compromise the antitumour response. Oncologists must be ready to detect and manage these new types of adverse events. This review focuses on the mechanisms of IRAE generation, putative relationship between dysimmune toxicity and antitumour efficacy, as a basis for management guidelines.

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Ewing sarcoma: The clinical relevance of the insulin-like growth factor 1 and the poly-ADP-ribose-polymerase pathway

Publication date: January 2016
Source:European Journal of Cancer, Volume 53
Author(s): Annemiek M. van Maldegem, Judith V.M.G. Bovée, Elleke F.P. Peterse, Pancras C.W. Hogendoorn, Hans Gelderblom
BackgroundIn the last three decades the outcome for patients with localised Ewing sarcoma (ES) has improved significantly since the introduction of multimodality primary treatment. However, for patients with (extra-) pulmonary metastatic and/or non-resectable relapsed disease the outcome remains poor and new treatment options are urgently needed. Currently the insulin-like growth factor 1 receptor (IGF-1R) pathway and the poly-ADP(adenosinediphosphate)-ribose-polymerase (PARP) pathway are being investigated for potential targeted therapies.IGF-1RThe IGF-1R pathway is known to be deregulated by the EWSR1-FLI1 translocation which makes it a potential target for therapy. Clinical trials have been reported in which only ES patients were treated with an IGF-1R inhibitor, either as single agent or in combination. In total 291 ES patients were included in these trials, in which two (0.7%) complete responses, 32 (11%) partial responses of which some durable, and 61 (21%) stable diseases were observed.PARPIn the presence of a PARP inhibitor DNA strand breaks cannot be efficiently repaired, leading to cell death. The first phase II trial with ES patients was recently published and showed no clinical responses, which may have been due to the drug being non-effective as a single agent.DiscussionThe IGF-1R pathway is an interesting target for ES and should be explored further, as biomarkers to select patients that might benefit from treatment are lacking. PARP inhibitors as single agent have so far failed to show improvement in outcome. Future directions include dual insulin receptor/IGF-1R blockade with linsitinib as well as chemotherapy–PARP combinations. Both therapeutic strategies are currently being explored.

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What are the top 10 physical activity research questions in schizophrenia?

What are the top 10 physical activity research questions in schizophrenia?

Disabil Rehabil. 2016 Jan 5;:1-9

Authors: Vancampfort D, Rosenbaum S, Probst M, Connaughton J, du Plessis C, Yamamoto T, Stubbs B

Abstract
Purpose Research has only recently started to consider the applicability of physical activity (PA) for people with schizophrenia. Although there is increasing evidence for the benefits of physical activity, this population remains generally physically inactive and sedentary. The aim of the current study is to highlight 10 pertinent physical activity research questions in people with schizophrenia. Method The International Organisation of Physical Therapy in Mental Health (IOPTMH) executed a consultation of its National Organisations (n = 13) to identify the most salient questions relevant to guide clinical practise on physical activity in people with schizophrenia. Results We identified the following 10 questions: (1) What are the benefits of physical activity for people with schizophrenia? (2) What are the mechanisms of the physical activity effects in people with schizophrenia? (3) What are the most prominent safety issues for physical activity prescription in people with schizophrenia? (4) What is the most optimal physical activity prescription for people with schizophrenia? (5) What are the key barriers for engaging people with schizophrenia in physical activity? (6) What are the most effective motivational interventions for physical activity adoption and maintenance in people with schizophrenia? (7) How do we translate physical activity research into clinical and community practise? (8) How can we ensure integration of physical therapists within the multidisciplinary mental health treatment team? (9) How can we prevent sedentary behaviour in people with schizophrenia? (10) What is the most appropriate physical activity assessment method in clinical practise? Conclusions Addressing these questions is critical for developing evidence-based approaches for promoting and sustaining an active lifestyle in people with schizophrenia. Ultimately, achieving this will improve the quality of life of this population. Implications for Rehabilitation Investigation of behaviour change interventions for people with schizophrenia is critical. A low cost, easy to use, clinical, valid physical activity questionnaire is urgently needed.

PMID: 26728764 [PubMed - as supplied by publisher]

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A qualitative investigation of factors that matter to individuals in the pain management process.

A qualitative investigation of factors that matter to individuals in the pain management process.

Disabil Rehabil. 2016 Jan 4;:1-9

Authors: Franklin ZC, Smith NC, Fowler NE

Abstract
OBJECTIVE: Chronic musculoskeletal pain is a complex condition to manage with widespread consequences including physical disability, psychosocial effects and increased use of healthcare. Previous research has found patients' experiences within health care can be influenced by factors such as expectations, therapist characteristics and treatment process. This study used patient interviews to identify the key factors that influence individuals' experiences in the management of chronic pain.
DESIGN: Qualitative study using semi-structured interviews in either a home or hospital setting.
METHODS: Semi-structured interviews were conducted on eight participants attending hospital-based pain management. Participants were asked about their experiences of pain management and living with a chronic pain condition. Interviews were transcribed and analysed thematically.
RESULTS: Three main themes were identified; impact of their condition on daily life, clinical interactions and the pain management process. Understanding the condition was a key factor for the patients, in particular, explanation by the clinician. The temporality of their pain meant timing of appointments was critical. Patients reported factors such as family days and follow-up sessions would improve their treatment experience.
CONCLUSIONS: This study highlighted important factors for healthcare professionals and patients in the management of chronic pain. Participants indicated a desire to understand their condition and learn strategies for self-management to allow them to cope better. As patients found benefit from being involved in the management process, discussions around the options for treatment may enhance management and rehabilitation. It is important we continue to research factors important to individuals with musculoskeletal pain to find an effective, evidence-based framework for understanding and managing this condition. Implications for rehabilitation This study highlights the importance to patients of being given information to help them understand their pain condition and to learn strategies for self-management to cope better. Where information was not provided and inadequate time allowed for questioning and discussion, patients tended to desire more frequent access to the care services. More effective communication may result in reduced demand and more efficient management. Patients suggested that ongoing peer support may offer an alternative to clinician-led services.

PMID: 26728636 [PubMed - as supplied by publisher]

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Support group programme for siblings of children with special needs: predictors of improved emotional and behavioural functioning.

Support group programme for siblings of children with special needs: predictors of improved emotional and behavioural functioning.

Disabil Rehabil. 2016 Jan 5;:1-10

Authors: Roberts RM, Ejova A, Giallo R, Strohm K, Lillie ME

Abstract
Purpose A pilot study to identify the predictors of improvement in emotional and behavioural functioning of siblings of children with special needs following participation in SibworkS, a six-week manual-based, cognitive-behavioural group programme. Method Data from 36 participants from a recent evaluation of the SibworkS programme was used. Measures were administered pre-intervention, immediately post-intervention and three months post-intervention. Treatment effects were measured using change scores for siblings on the Strengths and Difficulties Questionnaire - Parent Version (SDQ). Seven predictors were analysed: symptom severity of the child with special needs, participant age and gender, sibling birth order, family socio-economic status, participant baseline SDQ score and participant use of additional support services. Results The overall model significantly predicted change in SDQ scores at post-intervention and follow-up (adjusted R(2) = 0.41 and 0.40). At both evaluation points, SDQ change scores were significantly predicted by baseline SDQ score. Furthermore, symptom severity of the child with special needs was a significant predictor at three months post-intervention. Conclusions Poorer emotional and behavioural functioning among participants and symptom severity of the child with special needs were associated with greater intervention effects. These results indicate that SibworkS is likely to be beneficial for siblings who have difficulties adjusting, and siblings of children with more severe special needs. Implications for Rehabilitation Siblings of children with disability are at increased risk of emotional and behavioural difficulties. Sibworks is a manualised group-based intervention for the siblings of children with a disability. Poorer emotional and behavioural functioning among participants and symptom severity of the child with special needs were associated with greater intervention effects. SibworkS is likely to be beneficial for siblings who have difficulties adjusting and siblings of children with more severe disabilities.

PMID: 26728633 [PubMed - as supplied by publisher]

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Effects of modified constraint-induced movement therapy on the lower extremities in patients with stroke: a pilot study.

Effects of modified constraint-induced movement therapy on the lower extremities in patients with stroke: a pilot study.

Disabil Rehabil. 2016 Jan 4;:1-7

Authors: Zhu Y, Zhou C, Liu Y, Liu J, Jin J, Zhang S, Bai Y, Huang D, Zhu B, Xu Y, Wu Y

Abstract
PURPOSE: This study aimed to qualify the improvements of modified constraint-induced movement therapy (m-CIMT) on the lower limb of stroke patients via assessing the centre of mass (COM) displacement and the basic gait parameters.
METHODS: A total of 22 hemiplegic patients after stroke with first-time clinical cerebral infarction or haemorrhagic cerebrovascular accident were included in this study from May to December, 2014. The patients were randomly divided into m-CIMT group and the conventional therapy group (control group), and received corresponding training for five days/week for four weeks. The COM displacement and gait parameters were assessed by three-dimensional segmental kinematics method in pre-intervention and post- intervention therapy.
RESULTS: After four weeks of m-CIMT, the COM displacement on sagittal plane of paretic leg during stance phase was increased (pre: 91.04 ± 4.39 cm, post: 92.38 ± 4.58 cm, p < 0.05) and swing range of frontal plane was remarkably decreased (pre: 10.15 ± 3.05 cm, post: 7.83 ± 1.90 cm, p < 0.001). Meantime, the normalised swing range of COM in m-CIMT was superior to that in control group. Moreover, the gait parameters, including velocity (0.27 m/s), step width (0.10 m), step length (0.22 m) and swing time percentage (29.80%), were significantly improved by post-interventions of m-CIMT (p < 0.05).
CONCLUSION: The m-CIMT intervention improves the COM displacement in sagittal and frontal plane, as well as gait parameters. These suggest that m-CIMT intervention may be feasible and effective for the rehabilitation of hemiplegic gait. Implications for Rehabilitation Segmental kinematics method was used to estimate the displacement of the COM. m-CIMT interventions improved the COM displacement of patients after stroke. m-CIMT interventions improved the hemiplegic gait parameters.

PMID: 26728501 [PubMed - as supplied by publisher]

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