ABSTRACT
Chemoresistance in ovarian carcinoma is a puzzling issue that urges understanding of strategies used by cancer cells to survive DNA damage and to escape cell death. Expanding efforts to understand mechanisms driving chemoresistance and to develop alternative therapies targeting chemoresistant tumors are critical. Amplification of BRD4 is frequently associated with chemoresistant ovarian carcinoma, but little is known about the biological effects of the overexpression of BRD4 isoforms in this malignancy. Here, we described the consequences of BRD4-L and BRD4-S overexpression in ovarian carcinoma shedding a light on a complex regulation of BRD4 isoforms. We demonstrated that the BRD4-L transcript expression is required to generate both isoforms, BRD4-L and BRD4-S. We showed that the BRD4-S mRNA expression positively correlated with BRD4-S protein levels, while BRD4-L isoform showed negative correlation between mRNA and protein levels. Moreover, we demonstrated that an overexpression of BRD4 isoforms is associated with chemoresistance in ovarian cancer.
ABSTRACT
We discovered that the overexpression of mitochondrial enzyme succinate dehydrogenase (SDHA) is particularly prevalent in ovarian carcinoma and promotes highly metabolically active phenotype. Succinate dehydrogenase deficiency has been previously studied in some rare disorders. However, the role of SDHA upregulation and its impact on ovarian cancer metabolism has never been investigated, emphasizing the need for further research. We investigated the functional consequences of SDHA overexpression in ovarian cancer. Using proteomics approaches and biological assays, we interrogated protein content of metabolic pathways, cell proliferation, anchorage-independent growth, mitochondrial respiration, glycolytic function, and ATP production rates in those cells. Lastly, we performed a drug screening to identify agents specifically targeting the SDHA overexpressing tumor cells. We showed that SDHA overexpressing cells are characterized by enhanced energy metabolism, relying on both glycolysis and oxidative phosphorylation to meet their energy needs. In addition, SDHA-high phenotype was associated with cell vulnerability to glucose and glutamine deprivation, which led to a substantial reduction of ATP yield. We also identified an anti-metabolic compound shikonin with a potent efficacy against SDHA overexpressing ovarian cancer cells. Our data underline the unappreciated role of SDHA in reprogramming of ovarian cancer metabolism, which represents a new opportunity for therapeutic intervention.
ABSTRACT
OBJECTIVE: The study is a part of a prospective schizophrenia research project run in Krak6w. The general objective of the project is a long-time observation of people with schizophrenia, starting from the first episode through the years of living with the illness, the assessment of treatment results and predictors. The goal of this study was to investigate whether the level of expressed emotions in family at the onset of schizophrenia may have a prognostic value in regard to the further course of the illness. METHOD: Four indicators of treatment results were observed: the number of relapses, the overall time of inpatient hospitalisations, the number of inpatient hospitalisations and the severity of psychopathological symptoms, all in 3, 7 and 12 years since first hospitalisations. Expressed emotions (EE) were assessed with Camberwell Family Interview (CFI), the severity of symptoms was assessed with BPRS-SA, the UCLA version. RESULTS: (1) The increase of the number of relapses in subsequent follow-ups was more pronounced in the group of subjects with higher EE at the time of their first hospitalisations. (2) The number and overall time of hospitalisations did not correspond in any way with the EE level at the time of the first hospitalisation. (3) The dynamics of general and positive symptoms was related to the EE level at the time of the first hospitalisation. The negative syndrome was found to have no significant relationships. CONCLUSIONS: (1) The level of EE at the time of the first hospitalisation can be regarded as a specific predictor of relapses in the study group. (2) Creating research models that enable to differentiate: trait and state as well as dependent on family and on the course of illness aspects of EE, would enable better understanding of this phenomenon, which appears both as predictor and as effect of the course of schizophrenia.
Subject(s)
Expressed Emotion , Schizophrenia/rehabilitation , Schizophrenic Psychology , Adult , Analysis of Variance , Family/psychology , Family Relations , Female , Humans , Male , Personality Assessment/statistics & numerical data , Prospective Studies , Recurrence , Schizophrenia/physiopathology , Treatment Outcome , Young AdultABSTRACT
Basing on the example of one patient and her family, the system family consultation--as a way towards therapeutic dialogue--is presented. The patient was hospitalised due to schizophrenia. In the given example, the psychiatrist was an observer of the consultation conducted by the psychologist. A system therapy consultation allowed a "multiple-picture" to be obtained: the family members and the patient presented their own understanding of the situation. This new multi-perspective description--showing the patient's symptoms functionality caused diagnostic uncertainty in the psychiatrist--how far is the diagnosis of schizophrenia a justifiable one. According to the authors, the systemic consultation, giving the possibility to empathize with existential, psychological and family problems of the patient, leads to a dialogue with his/her family and it plays one of the most important roles in the therapeutic and diagnostic process.
Subject(s)
Family/psychology , Inpatients , Physician's Role , Professional-Family Relations , Schizophrenia, Paranoid/diagnosis , Schizophrenia, Paranoid/therapy , Schizophrenic Psychology , Adult , Clinical Competence , Diagnosis, Differential , Family Relations , Female , Humans , Poland , Professional-Patient Relations , Psychiatric Department, Hospital/organization & administration , Referral and Consultation , Treatment OutcomeABSTRACT
Basing on the example of one patient and her family, the advantages and disadvantages of a systemic consultation are presented. The patient was hospitalised due to schizophrenia. In the given example the psychiatrist was an observer of the consultation conducted by a therapist from the ward. A systemic consultation allowed a "multiple-picture" to be obtained: the family members and the patient presented their own understanding of the situation, their "stories" This new and multi-perspective description, showing the patient's symptoms functionality caused diagnostic uncertainty in the psychiatrist--how far is the diagnosis of schizophrenia a justifiable one. The possibility to empthasize with the existential, psychological and family problems of the patient caused a scepticism in the psychiatrist, towards the stigmatizing diagnosis. The authors stress the danger arising in the systemic consultation, which broadens and deepens the knowledge on the patient's situation. According to the authors, the systemic consultation is necessary to understand the social context of the patient and to formulate a complex treatment plan. At the same time however, the multiple layered perspective (which contains the psychological, social and existential domains of the patient) should not over-shadow the psychopathological domain. For the therapeutic team, the consideration of the given levels of systemic reality description remains a challenge.
Subject(s)
Family/psychology , Physician's Role , Referral and Consultation , Schizophrenia, Paranoid/diagnosis , Schizophrenia, Paranoid/therapy , Schizophrenic Psychology , Adult , Clinical Competence , Diagnosis, Differential , Family Relations , Female , Humans , Professional-Patient Relations , Time Factors , Treatment OutcomeABSTRACT
The paper presents the role of systemic consultation in the diagnostic and therapeutic process of the people hospitalised for the first time because of a psychotic episode. The following questions are going to be put: What is the role of systemic family consultation in the diagnostic and therapeutic process on the inpatient ward? What are the differences between systemic consultation and others forms of family interventions f.e. family interviews, psycho--education, systemic therapy? What are possibilities and limitations of consultation? What does it invite to? These are only some of those questions, which are typical for daily clinical practice, in which the family consultation takes an important part. In this paper according to our clinical experience, we would like to share some of our thoughts on the questions put. In spite of difficulties the family consultation confronts us with, we are deeply convinced that it has an important part in therapeutic and diagnostic process.
