Description:
Literature attests to the fact that psychosocial needs for cancer patients are not being adequately addressed. The tools, frameworks and guidelines developed, reflect differing professional perspectives and models of disease. Most studies have usually looked at what is happening from the patient and family's viewpoint in terms of medical and other needs. New national initiatives in psychosocial care include the organisation of nationwide practitioner workshops to encourage the implementation of the Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer. These guidelines focus mainly on the emotional and existential areas of need. The aim of this study was to: understand how a diversity of approaches and professional perspectives play out in everyday practice within a rural context; see how issues of distance and access affect this process; and highlight the deficiencies in the delivery of psychosocial services for cancer patients in rural Victoria. The study involved 59 questionnaire respondents (a 71% response rate), from which two interviews and six focus group discussions were drawn. Key findings were: regional and metropolitan hospitals and specialists not referring for support services; private patients missing out; general practitioners not referring to support services; late referrals to palliative care and district nursing; haphazard continuity of care for support needs of patients; and disputed responsibility for initial assessment.
Description:
Literature attests to the fact that psychosocial needs for cancer patients are not being adequately addressed. The tools, frameworks and guidelines developed, reflect differing professional perspectives and models of disease. Most studies have usually looked at what is happening from the patient and family's viewpoint in terms of medical and other needs. New national initiatives in psychosocial care include the organisation of nationwide practitioner workshops to encourage the implementation of the Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer. These guidelines focus mainly on the emotional and existential areas of need. The aim of this study was to: understand how a diversity of approaches and professional perspectives play out in everyday practice within a rural context; see how issues of distance and access affect this process; and highlight the deficiencies in the delivery of psychosocial services for cancer patients in rural Victoria. The study involved 59 questionnaire respondents (a 71% response rate), from which two interviews and six focus group discussions were drawn. Key findings were: regional and metropolitan hospitals and specialists not referring for support services; private patients missing out; general practitioners not referring to support services; late referrals to palliative care and district nursing; haphazard continuity of care for support needs of patients; and disputed responsibility for initial assessment.
Description:
PURPOSE: Cognitive-existential group therapy (CEGT) was developed to improve mood and mental attitude toward cancer in women with early-stage breast cancer receiving adjuvant chemotherapy. Given the debate about group therapy's association with increased survival in women with metastatic breast cancer, we were curious to check its effect at a much earlier stage in the cancer journey. PATIENTS AND METHODS: We randomly assigned 303 women with early-stage breast cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly group therapy plus three relaxation classes (n = 154) or to a control condition of three relaxation classes alone (n = 149). The primary outcome was survival. RESULTS: CEGT did not extend survival; the median survival time was 81.9 months (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI, 67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35 (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node status were significant predictors of survival. Low-grade histology yielded a hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node-negative status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78). CONCLUSION: CEGT does not prolong survival in women with early-stage breast cancer.
Description:
Objective: The objective is to investigate the influence of characteristics related to place of residence (self-reliance and stoicism) on men's intentions to use a telephone support service following radical prostatectomy. Methods: A community sample of 447 prostate cancer patients (31% response), recruited via Medicare Australia, completed a survey to assess levels of self-reliance and stoicism, and beliefs about addressing emotional distress through using telephone support services. Results: Results indicated that the model was a partially mediated model. Geographic remoteness was directly related to intention, and indirectly related through stoicism and subjective norms. Conclusion: Men from rural and remote areas in Australia might face particular challenges in seeking support following treatment for prostate cancer. These challenges appear to relate to the influence of stoic attitudes and normative expectations, than to issues of access and availability. Addressing stoic attitudes in the clinical setting, through normalising emotional reactions to cancer diagnosis and treatment, and the act of help-seeking for emotional support, may be beneficial.Sons, Ltd.
Description:
The objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer. Semi-structured qualitative interviews were conducted with 50 women at two time points (baseline and 6 months later). The interviews examined emotions, experiences, attitudes to sexual and continence issues and treatment decision making. As part of a larger prospective observational study, demographic data and scores for depression and anxiety were collected. Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months. In contrast, the 39 women in the non-distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves, appraisal of coping strategies and reappraisal of the situation. A surprise finding was the high level of resilience displayed by majority of these women. Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples.
My Road Ahead study protocol: A randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer
Description:
Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function.
Description:
The WHO classification subdivides large granular lymphocytic leukemias (LGLLs) into two subtypes, T and natural killer (NK) LGLLs, with distinct immunophenotypes and clinical presentations.1 Although arising from a common progenitor cell, NK cells are bone marrow–derived innate immune cells capable of cytokine production and cytotoxicity, and T cells are thymic-derived, antigen-specific lymphocytes that express a T-cell receptor (TCR).2 Natural killer T (NKT) cells, a subset of T cells, express NK-associated antigens such as CD16, CD56, and CD57, in addition to a CD1d-restricted, semi-invariant TCR.3 The point at which NKT cells branch from other TCR rearranged cells is not clearly defined. However, this is believed to be mediated through CD1d thymic-dependant signaling in CD4 CD8 double-positive thymocyte precursors.4,5 NK LGLL has a CD3−, CD8+, CD16+, CD56+ phenotype, with variable expression of CD57. It presents in teenagers and young adults with “B” symptoms, lymphadenopathy, hepatosplenomegaly, lymphocytosis, anemia, and thrombocytopenia and typically follows an aggressive clinical course.6 T-cell LGLLs are CD3+, CD8+, CD16+ with a clonal TCR rearrangement and defective Fas (CD95) -mediated apoptosis.7,8 Median age of onset is 55 years, presenting with splenomegaly, neutropenia, and recurrent infections. It is associated with rheumatoid arthritis and follows an indolent and protracted clinical course.9 We describe the case of a teenage patient with T-cell LGLL, who despite having a CD56 immunophenotype, initially showed an aggressive clinical course more in keeping with an NKT leukemia. We discuss the reasoning behind his conservative management and the observed changes in lymphocyte count and serum cytokine/chemokine levels over an 18-month period. There have been no reported cases of an initially aggressive presentation with subsequent spontaneous regression.
Description:
Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
Description:
Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells : Perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells
Description:
Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
Description:
Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
Paclitaxel-induced Src activation is inhibited by dasatinib treatment, independently of cancer stem cell properties, in a mouse model of ovarian cancer
Description:
Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.
Description:
Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.
Description:
Purpose: The purpose of this paper is to explore how university fieldtrips progressively deepen student engagement, and explain that stage-by-stage using the organismic integration theory. Design/methodology/approach: Using reflective logs, follow-up focus groups after two years and facilitator observations, this Malaysian qualitative study followed 12 business students across two three-day rainforest fieldtrips. Findings: Students progressed toward greater – and enduring – engagement, and transferable socio-cognitive skills, via three thematic stages. Voice and self-reflection – motivated by protecting group harmony – were key, enabled by facilitator and peer encouragement. Research limitations/implications: This exploratory study invites research in specified education cultures. Further, a longitudinal, quantitative study could be designed to examine the conceptual framework developed in Figure 1. Practical implications: University curricula, especially in collectivist high power distance cultures, should include fieldtrips as a particularly powerful form of experiential learning. Benefits of deeper engagement extend beyond present to future courses and the workplace. Higher student attraction/retention and employability may follow. Intrinsic motivation grows through the student–instructor interaction, watching theoretical principles in action, and having eureka moments through reflection, expression and exchange of ideas. Originality/value: The research fills a gap by mapping student engagement progressively from extrinsic to intrinsic motivation along with socio-cognitive competencies. The authors reveal the centrality of voice and reflection to promote group harmony, explain the roles of facilitators and peers and show long-lasting transferable benefits to learning. Novelly, the authors provide empirical support for existing conceptual frameworks but also extend these.