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OBJECTIVE: Psychosocial interventions directed to couples where one has advanced cancer can reduce distress, enhance communication, and provide an opportunity for relational growth. The present study aimed to develop an intervention to facilitate communication about living with advanced cancer using the Patient Dignity Inventory (PDI) as the focus of a clinical interview with couples toward the end of life. METHOD: Couples were recruited from oncology and palliative care services at a Sydney hospital. After the PDI was developed and manualized as an intervention for couples, the PDI-Couple Interview (PDI-CI) was delivered by a clinical psychologist and comprised the following: (1) the patient completed the PDI; (2) the patient's identified partner completed the PDI about how they thought the patient was feeling; and (3) the clinician reviewed the results with the couple, summarizing areas of concurrence and discordance and facilitating discussion. RESULTS: Some 34 couples were referred, of which 12 consented, 9 of whom completed the clinical interview. Reported benefits included enabling couples to express their concerns together, identifying differences in understanding, and giving "permission to speak" with each other. The focus of the interview around the PDI provided a structure that was particularly acceptable for men. Most couples confirmed that they were "on the same page," and where differences were identified, it provided a forum for discussion and a mutual understanding of the challenges in managing advanced cancer within a supportive context. SIGNIFICANCE OF RESULTS: Participant couples' experiences of the PDI-CI provide valuable insight into the benefits of this intervention. This preliminary study indicates that the intervention is a relatively simple means of enhancing closer communication and connection between couples where one has advanced cancer and may be an important adjunct in helping prepare couples for the challenges inherent toward the end of life. Further investigation of feasibility with a larger sample is recommended.
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Cuidadores/psicología , Terapia de Parejas/métodos , Neoplasias/psicología , Apoyo Social , Esposos/psicología , Estrés Psicológico/prevención & control , Enfermo Terminal/psicología , Anciano , Instituciones Oncológicas , Comunicación , Femenino , Humanos , Relaciones Interpersonales , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Personeidad , Proyectos Piloto , Psicometría , Estrés Psicológico/etiología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study explored how patients diagnosed with advanced cancer cope with an uncertain disease trajectory. SUBJECTS: 27 patients with advanced cancer and with a prognosis of 12â months or more were recruited from the medical/radiation oncology and palliative care service at three metropolitan hospitals. METHODS: A semistructured face-to-face interview was conducted. Interviews were audio-taped and transcribed verbatim. Data analysis was based on Grounded Theory using the constant comparison method. RESULTS: Results indicate that patients cope by avoidance, remaining positive, maintaining as normal a life as possible, minimising the impact of the disease on their daily lives, comparing themselves favourably with others in a similar situation and focusing on the outcome of treatment to control disease progression. Most did not wish to discuss prognosis or have detailed information on disease progression. CONCLUSIONS: Participants in this study represent an emerging cancer patient population who are receiving palliative therapies. While they have incurable cancer, they self-report as clinically well, they describe a good quality of life and the trajectory of their disease, while unpredictable, may extend over many months to years. Our study suggests that a flexible model of care is needed to support the needs of people who may still be receiving some form of chemotherapy and/or radiotherapy, and remain well. This model may need to take more of an intermittent approach, that is, as required for specific symptom management, rather than patients being linked continuously to a palliative care service for long periods of time.
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Adaptación Psicológica , Progresión de la Enfermedad , Neoplasias/psicología , Neoplasias/terapia , Cuidados Paliativos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Adulto JovenRESUMEN
Although the survival of breast cancer (BC) patients has increased over the last two decades due to improved screening programs and postoperative adjuvant systemic therapies, many patients die from metastatic relapse. Current biomarkers used in the clinic are not useful for the early detection of BC, or monitoring its progression, and have limited value in predicting response to treatment. The development of proteomic techniques has sparked new searches for novel protein markers for many diseases including BC. Proteomic techniques allow for a high-throughput analysis of samples with the visualization and quantification of thousands of potential protein and peptide markers. Human urine is one of the most interesting and useful biofluids for routine testing and provides an excellent resource for the discovery of novel biomarkers, with the advantage over tissue biopsy samples due to the ease and less invasive nature of collection. In this review, we summarize the results from studies where urine was used as a source for BC biomarker research and discuss urine sample preparation, its advantage, challenges, and limitation. We focus on the gel-based proteomic approaches as well as the recent development of quantitative techniques in BC urine biomarker detection. Finally, the future use of modern proteomic techniques in BC biomarker identification will be discussed.
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Biomarcadores de Tumor/orina , Neoplasias de la Mama/diagnóstico , Proteómica/métodos , Neoplasias de la Mama/orina , Femenino , Humanos , Espectrometría de Masas , Manejo de EspecímenesRESUMEN
There is currently no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastatic disease remain the main causes of treatment failure and mortality in CaP patients. Although several advances have been made in the control of CRPC with some newly developed drugs, there is still an urgent need to investigate the mechanisms and pathways of prostate cancer (CaP) metastasis and chemoresistance, identify useful therapeutic targets, develop novel treatment approaches, improve current therapeutic modalities and increase patients' survival. Cancer stem cells (CSCs), a minority population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer recurrence but also contribute substantially to chemoresistance. As such, a number of mechanisms in chemoresistance have been identified to be associated with CSCs. Therefore, a thorough and integral understanding of these mechanisms can identify novel biomarkers and develop innovative therapeutic strategies for CaP treatment. Our recent data have demonstrated CSCs are associated with CaP chemosensitivity. In this review, we discuss the roles of putative CSC markers in CaP chemoresistance and elucidate several CSC-associated signaling pathways such as PI3K/Akt/mTOR, Wnt/ß-catenin and Notch pathways in the regulation of CaP chemoresistance. Moreover, we will summarize emerging and innovative approaches for the treatment of CRPC and address the challenging CRPC that is driven by CSCs. Understanding the link between CSCs and metastatic CRPC will facilitate the development of novel therapeutic approaches to overcome chemoresistance and improve the clinical outcomes of CaP patients.
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Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Femenino , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
INTRODUCTION: Prostate cancer (CaP) is the second leading malignancy in older men in Western countries. The role of CD44 variant 6 (CD44v6) in CaP progression and therapeutic resistance is still uncertain. Here, we investigated the roles of CD44v6 in CaP metastasis and chemo/radioresistance. Expression of CD44v6 in metastatic CaP cell lines, human primary CaP tissues and lymph node metastases was assessed using immunofluorescence and immunohistochemistry, respectively. METHODS: Knock down (KD) of CD44v6 was performed in PC-3M, DU145, and LNCaP cells using small interfering RNA (siRNA), and confirmed by confocal microscope, Western blot and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The adhesive ability and invasive potential were assessed using a hyaluronic acid (HA) adhesion and a matrigel chamber assay, respectively. Tumorigenesis potential and chemo-/radiosensitivity were measured by a sphere formation assay and a colony assay, respectively. RESULTS: Over-expression of CD44v6 was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of CD44v6 suppressed CaP proliferative, invasive and adhesive abilities, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated epithelial-mesenchymal transition (EMT), PI3K/Akt/mTOR, and Wnt/ß-catenin signaling pathway proteins in vitro. CONCLUSIONS: Our findings demonstrate that CD44v6 is an important cancer stem cell-like marker associated with CaP proliferation, invasion, adhesion, metastasis, chemo-/radioresistance, and the induction of EMT as well as the activation PI3K/Akt/mTOR and Wnt signaling pathways, suggesting that CD44v6 is a novel therapeutic target to sensitize CaP cells to chemo/radiotherapy.
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Receptores de Hialuranos/metabolismo , Metástasis Linfática/genética , Neoplasias de la Próstata/metabolismo , Línea Celular Tumoral , Proliferación Celular , Humanos , Receptores de Hialuranos/genética , Metástasis Linfática/patología , Masculino , Fosforilación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
We report upon the design, content and feedback from an interactive, experiential series of Workshops in Healing for senior medical students. Fifty-six final year medical students enrolled in 2×3â h workshops designed around the core themes of 'physician know thyself' (Workshop 1) and 'confronting suffering' (Workshop 2). Of the 56 students who initially enrolled, 48 students completed both workshops and provided a written open-ended reflection of their learning experience. The study, undertaken over a consecutive 5-year period (2008-2012), employed an emergent, qualitative design using thematic analysis of the reflective comments. We found that the design and content of both workshops promoted transformative learning for these final year medical students. Students identified the following benefits: (1) the opportunity to reaffirm their commitment to their chosen career path; (2) the value of listening to other students share their stories; (3) the importance of the timing of the workshops to occur after exams; (4) the use of various mediums such as art, poetry, music and contemporary/classic literature to present concepts of suffering and healing; and (5) the creation of a safe and confidential space. Students reported that these innovative workshops gave them a renewed sense of drive and enthusiasm for their chosen career. They highlighted the importance of addressing an aspect of medicine (healing) not covered in the traditional medical curriculum. Workshops in Healing helped them to rediscover a deeper meaning to medicine and their roles as future healthcare professionals.
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Curriculum , Educación de Pregrado en Medicina , Empatía , Aprendizaje , Estrés Psicológico , Estudiantes de Medicina , Selección de Profesión , Humanidades , HumanosRESUMEN
Radiation therapy (RT) continues to be one of the most popular treatment options for localized prostate cancer (CaP). Local CaP recurrence after RT is a pattern of treatment failure attributable to radioresistance of cancer cells. One major obstacle to RT is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Recent results indicate that phosphoinositide 3-kinase (PI3K)/Akt/phosphatase and tensin homolog (PTEN)/mammalian target of rapamycin (mTOR) signaling pathway, autophagy, epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are involved in CaP metastasis and radioresistance. Emerging evidence also suggests that combining a radiosensitizer with RT increases the efficacy of CaP treatment. Understanding the mechanisms of radioresistance will help to overcome recurrence after RT in CaP patients and prevent metastasis. In this review, we discuss the novel findings of PI3K/Akt/PTEN/mTOR signaling pathway, autophagy, EMT and CSCs in the regulation of CaP metastasis and radioresistance, and focus on combination of radiosensitizers with RT in the treatment of CaP in preclinical studies to explore novel approaches for future clinical trials.
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Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Tolerancia a Radiación , Animales , Autofagia , Terapia Combinada , Transición Epitelial-Mesenquimal , Humanos , Masculino , Metástasis de la Neoplasia , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de la radiación , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/terapia , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Prostate cancer (CaP) is the second leading malignancy in men. The role of epithelial cell adhesion molecule (EpCAM), also known as CD326, in CaP progression and therapeutic resistance is still uncertain. Here, we aimed to investigate the roles of EpCAM in CaP metastasis and chemo/radioresistance. Expression of EpCAM in CaP cell lines and human CaP tissues was assessed using immunofluorescence and immunohistochemistry, respectively. EpCAM was knocked down (KD) in PC-3, DU145 and LNCaP-C4-2B cells using small interfering RNA (siRNA), and KD results were confirmed by confocal microscope, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The invasive potential was assessed using a matrigel chamber assay. Tumorigenesis potential was measured by a sphere formation assay. Chemo-/radiosensitivity were measured using a colony formation assay. Over-expression of EpCAM was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of EpCAM suppressed CaP proliferation and invasive ability, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated E-cadherin, p-Akt, p-mTOR, p-4EBP1 and p-S6K expression in CaP cells. Our findings suggest that EpCAM plays an important role in CaP proliferation, invasion, metastasis and chemo-/radioresistance associated with the activation of the PI3K/Akt/mTOR signaling pathway and is a novel therapeutic target to sensitize CaP cells to chemo-/radiotherapy.
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Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/terapia , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Antígenos de Neoplasias/genética , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos , Molécula de Adhesión Celular Epitelial , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/patología , Tolerancia a Radiación , Transducción de Señal , TransfecciónRESUMEN
Radiation therapy (RT) continues to be one of the most popular treatment options for localized prostate cancer (CaP). The purpose of the study was to investigate the in vitro effect of LBH589 alone and in combination with RT on the growth and survival of CaP cell lines and the possible mechanisms of radiosensitization of this combination therapy. The effect of LBH589 alone or in combination with RT on two CaP cell lines (PC-3 and LNCaP) and a normal prostatic epithelial cell line (RWPE-1) was studied by MTT and clonogenic assays, cell cycle analysis, western blotting of apoptosis-related and cell check point proteins, and DNA double strand break (DSB) repair markers. The immunofluorescence staining was used to further confirm DSB expression in treated CaP cells. Our results indicate that LBH589 inhibited proliferation in both CaP and normal prostatic epithelial cells in a time-and-dose-dependent manner; low-dose of LBH589 (IC20) combined with RT greatly improved efficiency of cell killing in CaP cells; compared to RT alone, the combination treatment with LBH589 and RT induced more apoptosis and led to a steady increase of sub-G1 population and abolishment of RT-induced G2/M arrest, increased and persistent DSB, less activation of non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathways and a panel of cell cycle related proteins. These results suggest that LBH589 is a potential agent to increase radiosensitivity of human CaP cells. LBH589 used either alone, or in combination with RT is an attractive strategy for treating human CaP.
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Inhibidores de Histona Desacetilasas/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Indoles/uso terapéutico , Neoplasias de la Próstata/patología , Western Blotting , Ciclo Celular/efectos de los fármacos , Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Terapia Combinada , Daño del ADN , Citometría de Flujo , Humanos , Masculino , Panobinostat , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Recombinación GenéticaRESUMEN
The aims of this study were to evaluate the impact of cosmetic and functional outcomes after breast-conserving surgery (BCS) and radiation on quality of life (QOL). In this exploratory analysis; baseline, 5 and 10 years data of patient's assessment of breast cosmesis, arm swelling/pain, limitation of movement, loss of feeling in fingers and breast sensitivity/tenderness were dichotomized and their impact on QOL (QLQ-C30) were assessed. Multivariable modelling was also performed to assess associations with QOL. The St. George and Wollongong randomized trial randomized 688 patients into the boost and no boost arms. 609, 580, and 428 patients had baseline, 5 and 10 years cosmetic data available, respectively. Similar numbers had the various functional assessments in the corresponding period. By univariate analysis, cosmesis and a number of functional outcomes were highly associated with QOL. Adjusted multivariate modelling showed that cosmesis remained associated with QOL at 5 and 10 years. Breast sensitivity, arm pain, breast separation, age and any distant cancer event were also associated with QOL on multivariate modelling at 10 years. This study highlights the importance of maintaining favorable cosmetic and functional outcomes following BCS. In addition, the clinically and statistically significant relationship between functional outcomes and QOL shows the importance for clinicians and allied health professionals in identifying, discussing, managing, and limiting these effects in women with breast cancer in order to maintain QOL.
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Neoplasias de la Mama/psicología , Estética/psicología , Calidad de Vida , Recuperación de la Función , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Mastectomía Segmentaria/efectos adversos , Persona de Mediana Edad , Dolor/epidemiología , Dolor/etiología , Dolor/psicología , Radioterapia/efectos adversos , Procedimientos de Cirugía Plástica , Tiempo , Adulto JovenRESUMEN
The tear film covers and protects the ocular surface. It contains various molecules including a large variety of proteins. The protein composition of the tear fluid can change with respect to various local and systemic diseases. Prior to the advent of the proteomic era, tear protein analysis was limited to a few analytical techniques, the most common of which was immunoelectrophoresis, an approach dependent on antibody availability. Using proteomics, hundreds of tear proteins could potentially be identified and subsequently studied. Although detection of low-abundance proteins in the complex tear proteome remains a challenge, advances in sample fractionation and mass spectrometry have greatly enhanced our ability to detect these proteins. With increasing proteomic applications, tears show great potential as biomarkers in the development of clinical assays for various human diseases. In this chapter, we discuss the structure and functions of the tear film and methods for its collection. We also summarize potential tear protein biomarkers identified using proteomic techniques for both ocular and systemic diseases. Finally, modern proteomic techniques for tear biomarker research and future challenges are explored.
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Conjuntivitis Alérgica/diagnóstico , Síndromes de Ojo Seco/diagnóstico , Proteínas del Ojo/aislamiento & purificación , Proteómica , Lágrimas/química , Biomarcadores/análisis , Estudios de Casos y Controles , Conjuntivitis Alérgica/metabolismo , Conjuntivitis Alérgica/patología , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/patología , Electroforesis en Gel Bidimensional , Proteínas del Ojo/metabolismo , Humanos , Aparato Lagrimal/metabolismo , Aparato Lagrimal/patología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The purpose of this study was to investigate the effect of combination of LBH589 with docetaxel (DTX) on the growth and survival of epithelial ovarian cancer (EOC) cells in vitro and the possible mechanisms of chemo-sensitization of LBH589 in the combination treatment. The effect of LBH589 alone or in combination with DTX on four EOC cell lines (OVCAR-3, IGROV-1, A2780 and SKOV-3) was studied by MTT and clonogenic assays, acridine orange (AO)/ethidium bromide (EB) staining for apoptosis, Western blotting for apoptosis-related proteins, histone H3 and H4 proteins, DNA double strand break (DSB) repair marker and phosphorylation of Akt. LBH589 alone inhibited EOC cell proliferation in a time and dose-dependent manner. Low-dose of LBH589 (IC(20)) combined with DTX had an additive effect and greatly improved efficacy of DTX cell killing in EOC cells. Compared to DTX alone, the combination treatment with LBH589 and DTX induced more apoptosis and led to an increased and persistent DSB. Cell death following single or combined treatment was associated with the release of cytochrome c activity, increased caspase-3 (active) and PARP-1(cleaved), histone acetylation-related proteins and PI3k/Akt signaling pathway. Our results suggest that LBH589 enhances DTX-induced apoptosis in human EOC cells, and can be used in combination with DTX as an attractive strategy for treating human EOC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Indoles/farmacología , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Taxoides/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Epitelial de Ovario , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Docetaxel , Relación Dosis-Respuesta a Droga , Femenino , Inhibidores de Histona Desacetilasas/administración & dosificación , Histonas/metabolismo , Humanos , Ácidos Hidroxámicos/administración & dosificación , Indoles/administración & dosificación , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Panobinostat , Transducción de Señal/efectos de los fármacos , Taxoides/administración & dosificaciónRESUMEN
CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP) cells, their docetaxel (DTX) responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD) in PC-3M-luc CaP cells using short hairpin RNA (shRNA). Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2) and MCT4 (monocarboxylate tranporter-4) was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c.) xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment.
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Antineoplásicos/farmacología , Basigina/biosíntesis , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Receptores de Hialuranos/biosíntesis , Proteínas de Neoplasias/metabolismo , Neoplasias de la Próstata/metabolismo , Taxoides/farmacología , Animales , Basigina/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Docetaxel , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Receptores de Hialuranos/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Trasplante Heterólogo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The authors propose that the characteristics of personal (individual) compassion may be extrapolated to the concept of corporate (organizational) compassion. Modern health care facilities attract staff members who are able to exercise varying degrees of compassion in their busy daily routines. However, little discussion has taken place on how health care organizations might best harness and integrate aspects of individual compassion to create an organization with compassion as a core value. We define three characteristics of a "compassionate hospital" as 1) the presence of a healing environment, 2) a sense of connection among people, and 3) a sense of purpose and identity. We suggest how a "top down" focus on compassion as a core value by clinical leaders could maximize the compassion of health care workers, and reduce the suffering expressed and/or experienced by health care workers and patients in today's health care facilities. The compassionate hospital concept is intended to act as a proposition for health policy researchers and decision-makers in health care so as to reduce the suffering of sick patients, and to restore a sense of well-being, meaning, and purpose among health care workers.
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Empatía , Hospitales , Cultura Organizacional , Atención al Paciente/psicología , Humanos , Cuerpo Médico de Hospitales/psicología , Personal de Enfermería en Hospital/psicologíaRESUMEN
CD44 plays an important role in cancer metastasis, chemotherapy, and radiation resistance. The present study investigated the relationship of CD44 expression and radioresistance, and the potential mechanisms of CD44 in radiosensitivity using prostate cancer (CaP) cell lines. CD44 was knocked down in three CaP cell lines (PC-3, PC-3M-luc, and LNCaP) using small interfering RNA (siRNA) and clonogenic survival fractions after single dose irradiation were compared before and after CD44 knocking down (KD). The effect of radiation on cell cycle distribution was examined by flow cytometry and the cell cycle-related protein levels of phospho-Chk1 and phospho-Chk2 were ascertained by Western blotting. The expression of the DNA double strand break (DSB) marker-γH2AX was also quantified by immunofluorescence staining. Our results indicate that the down-regulation of CD44 enhanced radiosensitivity in PC-3, PC-3M-luc, and LNCaP CaP cells, the sensitizing enhancement ratio for these cell lines was 2.3, 1.3, and 1.5, respectively and that the delay of DNA DSB repair in low CD44-expressing KD CaP cells correlated with ineffective cell cycle arrest and the delayed phosphorylation of Chk1 and Chk2. These findings suggest that CD44 may be a valuable biomarker and a predictor of radiosensitivity in CaP treatment.
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Biomarcadores de Tumor/metabolismo , Receptores de Hialuranos/metabolismo , Neoplasias de la Próstata/patología , Tolerancia a Radiación , Biomarcadores de Tumor/genética , Ciclo Celular , Línea Celular Tumoral , Daño del ADN , Reparación del ADN , Humanos , Receptores de Hialuranos/genética , Masculino , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/radioterapia , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Two contemporary patient narratives provide an opportunity to reflect on the role of clinicians in the healing process, as seen in the works of Rembrandt and Michelangelo.
Asunto(s)
Arte/historia , Manejo del Dolor/métodos , Anciano , Resultado Fatal , Femenino , Historia del Siglo XV , Humanos , Masculino , Persona de Mediana Edad , Narración , Neoplasias/terapiaRESUMEN
MUC1 is associated with cellular transformation and tumorigenicity and is considered as an important tumor-associated antigen (TAA) for cancer therapy. We previously reported that anti-MUC1 monoclonal antibody C595 (MAb C595) plus docetaxel (DTX) increased efficacy of DTX alone and caused cultured human epithelial ovarian cancer (EOC) cells to undergo apoptosis. To further study the mechanisms of this combination-mediated apoptosis, we investigated the effectiveness of this combination therapy in vivo in an intraperitoneal (i.p.) EOC mouse model. OVCAR-3 cells were implanted intraperitoneally in female athymic nude mice and allowed to grow tumor and ascites. Mice were then treated with single MAb C595, DTX, combination test (MAb C595 and DTX), combination control (negative MAb IgG(3) and DTX) or vehicle control i.p. for 3 weeks. Treated mice were killed 4 weeks post-treatment. Ascites volume, tumor weight, CA125 levels from ascites and survival of animals were assessed. The expression of MUC1, CD31, Ki-67, TUNEL and apoptotic proteins in tumor xenografts was evaluated by immunohistochemistry. MAb C595 alone inhibited i.p. tumor growth and ascites production in a dose-dependent manner but did not obviously prevent tumor development. However, combination test significantly reduced ascites volume, tumor growth and metastases, CA125 levels in ascites and improved survival of treated mice compared with single agent-treated mice, combination control or vehicle control-treated mice (P<0.05). The data was in a good agreement with that from cultured cells in vitro. The mechanisms behind the observed effects could be through targeting MUC1 antigens, inhibition of tumor angiogenesis, and induction of apoptosis. Our results suggest that this combination approach can effectively reduce tumor burden and ascites, prolong survival of animals through induction of tumor apoptosis and necrosis, and may provide a potential therapy for advanced metastatic EOC.