SATB1-Mediated Upregulation of the Oncogenic Receptor Tyrosine Kinase HER3 Antagonizes MET Inhibition in Gastric Cancer Cells.

MET-amplified gastric cancer cells are extremely sensitive to MET inhibition in vitro, whereas clinical efficacy of MET inhibitors is disappointing. The compensatory activation of other oncogenic growth factor receptors may serve as an underlying mechanism of resistance. In this study, we analyzed the role of HER receptors, in particular HER3 and its ligand heregulin, in this respect. This also included the chromatin-organizer protein SATB1, as an established regulator of HER expression in other tumor entities. In a panel of MET-amplified gastric carcinoma cell lines, cell growth under anchorage-dependent and independent conditions was studied upon inhibitor treatment or siRNA-mediated knockdown. Expression analyses were performed using RT-qPCR, FACS, and immunoblots. Signal transduction was monitored via antibody arrays and immunoblots. As expected, MET inhibition led to a growth arrest and inhibition of MAPK signaling. Strikingly, however, this was accompanied by a rapid and profound upregulation of the oncogenic receptor HER3. This finding was determined as functionally relevant, since HER3 activation by HRG led to partial MET inhibitor resistance, and MAPK/Akt signaling was even found enhanced upon HRG+MET inhibitor treatment compared to HRG alone. SATB1 was identified as mediator of HER3 upregulation. Concomitantly, SATB1 knockdown prevented upregulation of HER3, thus abrogating the HRG-promoted rescue from MET inhibition. Taken together, our results introduce the combined HER3/MET inhibition as strategy to overcome resistance towards MET inhibitors.

To change or not to change - That is the question: A qualitative study of lifestyle changes following acute myocardial infarction.

Objective The purpose of this study was to investigate key factors related to lifestyle changes following acute myocardial infarction (AMI) by eliciting survivors' subjective needs for, attitudes towards and experiences with behaviour changes in their everyday life to improve future interventions promoting lifestyle changes. Methods Semi-structured interviews were conducted with 21 individuals who had recently experienced an AMI. The interviews were audio-recorded and transcribed verbatim. The data were analysed using qualitative content analysis. Results The data analysis revealed that lifestyle changes following AMI are influenced by a combination of individual (physical and psychological) and social factors that can be grouped into facilitators and barriers. The interviews indicated the need for more personalised information regarding the causes and risk factors of illness, the benefits of lifestyle changes and the importance of including significant others in lifestyle advice and education and of individualising support. Discussion Lifestyle change is a continuous process that is not completed within a few months after a cardiac event. Considering the identified themes when developing interventions to promote lifestyle changes following AMI may enhance the effectiveness and sustainability of such interventions.

Anxiety disorders in patients with implantable cardioverter defibrillators: frequency, course, predictors, and patients' requests for treatment.

OBJECTIVES: To determine (1) the frequency and course of anxiety disorders in patients with implantable cardioverter defibrillators (ICDs), (2) the predictors of anxiety, (3) the treatment situation and patients' requests for therapy. METHODS: Quantitative and qualitative methods in a prospective design. At baseline, 327 ICD outpatients completed validated self-report questionnaires (participation rate = 77%). Five months later, a predefined subsample of patients (n = 108, participation rate = 81%) consisting of all patients with (n = 58) and a randomly selected subsample of patients without (n = 50) elevated symptoms of anxiety at baseline, was reassessed using a structured diagnostic interview, the baseline questionnaires, and open-ended questions. RESULTS: At baseline, 19.2% of patients suffered from at least some form of clinically relevant anxiety with an overall remission rate of 56.5% at follow-up. Predictive for anxiety at follow-up were higher levels of stress (odds ratio [OR], 1.52, P < 0.001), depression (OR, 1.26, P < 0.001), somatic symptom severity (OR, 1.25, P < 0.001), more perceived ICD-related constraints (OR, 2.4, P = 0.007), lower quality of life (physical health: OR, 0.91, P = 0.004; mental health: OR, 0.87, P = 0.001), and a higher New York Heart Association class (OR, 7.99, P = 0.002) at baseline. Only 35.3% of patients received an evidenced-based treatment for their anxiety disorder. A supervised ICD patient group was the most preferred treatment (51.1%). CONCLUSIONS: Most patients seemed to adapt well to ICD therapy. Patients suffering from additional psychological strains and reporting more negative ICD-related attitudes were at risk for developing an anxiety disorder. Special tailored interventions, such as a supervised ICD patient group, could reduce the gap between treatment needs and the treatment situation.

A shared decision-making communication training program for physicians treating fibromyalgia patients: effects of a randomized controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMS) is a condition of chronic widespread pain that is difficult to control and is associated with strains in physician-patient interaction. Shared decision making (SDM) can be a potential solution to improve interaction. We evaluated the effects of an SDM intervention, including an SDM communication training program for physicians, in a randomized controlled trial with FMS patients. The main objective was to assess whether SDM improves the quality of physician-patient interaction from patients' perspective. METHODS: Patients were randomized to either an SDM group or an information-only group. The SDM group was treated by physicians trained in SDM communication and had access to a computer-based information package; the information-only group received only the information package and was treated by standard physicians. All patients were offered the same evidence-based treatment options for FMS. Patients were assessed with questionnaires on physician-patient interaction (main outcome criteria) and decisional processes. Physicians filled out a questionnaire on interaction difficulties. Assessment took place immediately after the initial consultation. RESULTS: Data from 85 FMS patients (44 in the SDM group and 41 in the information-only group) were analyzed. The mean age was 49.9 years (S.D.=10.2), and 91.8% of patients were female. The quality of physician-patient interaction was significantly higher in the SDM group than in the information-only group (P<.001). We found no differences in secondary outcome measures. CONCLUSIONS: SDM with FMS patients might be a possible means to achieve a positive quality of physician-patient interaction. A specific SDM communication training program teaches physicians to perform SDM and reduces frustration in patients.

Long-term effects of a shared decision-making intervention on physician-patient interaction and outcome in fibromyalgia. A qualitative and quantitative 1 year follow-up of a randomized controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMS) patients and their doctors frequently complain on interaction difficulties. We investigated the effects of a shared decision-making (SDM) intervention on physician-patient interaction and health outcome. METHODS: Sixty-seven FMS patients of an outpatient university setting that had been included in a randomized controlled trial were followed up. They were either treated in an SDM group or in an information group. Both groups saw a computer based information tool on FMS, but only the SDM group was treated by doctors which underwent a special SDM communication training. A comparison group of 44 FMS patients receiving treatment as usual was recruited in rheumatological practices. We assessed patients and their doctors using a combined qualitative and quantitative approach. Patients and doctors were followed-up after 3 months (T2) and after 1 year (T3). RESULTS: The significantly best quality of physician-patient interaction was reported by patients and doctors of the SDM group, followed by the information group. Coping had more often improved in the SDM group than in the information group. However directly health related outcome variables had not improved in any of the groups at T3. CONCLUSION: An SDM intervention can lead to an improved physician-patient relationship from the patients' and from the doctors' perspective. PRACTICE IMPLICATIONS: It should be considered to include SDM in standard care for FMS patients.

A computer-based information-tool for chronic pain patients. Computerized information to support the process of shared decision-making.

OBJECTIVE: Assessment of the use of a computerized information-tool in the context of a shared decision-making process with chronic pain patients. METHODS: In the scope of a prospective and randomized study on shared decision-making with Fibromyalgia patients, a total of 75 patients had access to computer-based information about their illness. Fibromyalgia is a condition of chronic wide-spread pain, belonging to rheumatism, which mainly affects mature female patients. The majority of the patients in our study are female (93%) with an average age of 50 years. The computer-based information-tool provided the patients with detailed information about pathogenesis, typical symptoms, treatment options and prognosis. Six evaluative questions were posed to the participants concerning the assessment of the information presented, the handling of the programme, the need for an introduction to the programme, the quality of the layout and the assessment of the length of time spent in front of the computer and the assessment of the usefulness of such a tool in general practitioners' offices. Furthermore, psychological self-assessment questionnaires were filled out by the participants. RESULTS: The patients highly appreciate the possibility of using computer-based information-tools and endorse the implementation of such tools in general practitioners' offices. CONCLUSION: Computerized information leads to a better understanding of the illness and the treatment options on the part of the patient. PRACTICAL IMPLICATIONS: For further practical use it is crucial to provide an introduction to the handling of a computer to unskilled patients.

Medical patients' attitudes toward emotional problems and their treatment. What do they really want?

BACKGROUND: Understanding medical patients' attitudes toward emotional problems and their management is crucial to overcoming obstacles to efficient depression treatment. OBJECTIVE: To investigate attitudes toward emotional problems, psychotherapy, antidepressants, alternative treatment approaches, and self-management techniques in depressed and nondepressed medical outpatients. DESIGN: Cross-sectional interview study, including quantitative and qualitative methods. PATIENTS: Eighty-seven depressed subjects (mean age, 41.0 years; 66% female) and 91 nondepressed subjects (mean age, 41.4 years; 67% female) from 7 internal medicine outpatient clinics and 12 family practices (participation rate, 91%). MEASUREMENTS: Depression diagnoses were established using a structured diagnostic interview, and patient attitudes were investigated with open-ended interview questions regarding treatment preferences, factors improving and impairing emotional well-being, and patients' self-management to improve well-being. RESULTS: Among the depressed patients, psychotherapy was the most frequently preferred treatment (29%) and the most common factor reported to improve emotional well-being (36%). Twenty-two percent of the depressed patients desired depression treatment within their current medical system, but requested substantially more time to communicate with their physician. Antidepressants were rarely mentioned as a preferred treatment (6%) or factor improving well-being (11%). Thirty-eight percent of the depressed patients attributed their impaired mood to health problems. Compared with the depressed patients, the nondepressed controls preferred significantly less frequent depression-specific therapies. CONCLUSIONS: The vast majority of medical outpatients prefer treatment approaches for emotional problems that go beyond antidepressant medication therapy. Health care providers should consider providing sufficient time to communicate with their patients, the strong preference for psychotherapy, and an appropriate treatment of comorbid physical conditions.

[The process of shared decision making in chronic pain patients. Evaluation and modification of treatment decisions]. / Der Prozess der partizipativen Entscheidungsfindung bei chronischen Schmerzpatienten. Evaluation und Modifikation von Therapieentscheidungen.

Conditions affecting the musculoskeletal system are the cause of approximately 25% of absenteeism from work. Fibromyalgia syndrome is an exemplary condition of chronic widespread pain which most physicians consider difficult to manage. The physician-patient relationship is burdened with resignation and frustration on both sides. Initial agreement regarding the aims of treatment is rare. The patient's active involvement in the decision making process is expected to improve the physician-patient relationship. One aspect of this shared decision making process is the evaluation and possibly modification of treatment decisions. In the present study 39 consultations of physicians who had undergone special communication training were examined as to whether these physicians actually exercised the option of revising their treatment decisions. In 87.2% of the consultations the therapy decisions were modified within three months after the first encounter. Patients considered to be "difficult" were less likely to modify their decisions. The shared decision making process usually takes more than one consultation.