Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decision making concerning patients with end stage cancer is a challenging process. Since quality of life is a very important issue for patients with short-term life expectancy, benefits of antitumor therapy and possible negative side effects have to be considered carefully. The patient's desires play a pivotal role in the final decision. Informed consent becomes even more difficult when the competence of a patient in choosing treatment is questionable. In this case report, a 60 year old female patient with exulcerating breast cancer, brain metastases and long-term untreated schizophrenia refuses antitumor treatment. How can the palliative care team make the best possible decision on her behalf? Medical, ethical and legal aspects are discussed.
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PMID:[Joint decision making--a challenge. A psychiatric patient with end-stage cancer refuses antitumor treatment]. 1683 Feb 45

The ErbB family of four receptor tyrosine kinases occupies a central role in a wide variety of biological processes from neuronal development to breast cancer. New information continues to expand their biologic significance and to unravel the molecular mechanisms that underlie the signaling capacity of these receptors. Here, we review several aspects of ErbB receptor physiology for which new and significant information is available. These include ligand-dependent receptor dimerization and kinase activation, which is a prerequisite for all subsequent growth factor-dependent cell responses. We also address novel roles of receptor fragments in signaling, trafficking to intracellular sites, such as the nucleus, and ErbB roles in non-cancer disease processes, including schizophrenia, chronic renal disease, hypertension, and the cellular entry of infectious pathogens.
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PMID:ErbB receptors: new insights on mechanisms and biology. 1708 50

Neuregulins (NRGs) comprise a large family of EGF-like signaling molecules involved in cell-cell communication during development and disease. The neuregulin family of ligands has four members: NRG1, NRG2, NRG3, and NRG4. Relatively little is known about the biological functions of the NRG2, 3, and 4 proteins. In contrast, the NRG1 proteins have been demonstrated to play important roles during the development of the nervous system, heart, and mammary glands. For example, NRG1 has essential functions in the development of neural crest cells and some of their major derivatives, like Schwann cells and sympathetic neurons. NRG1 controls the trabeculation of the myocardial musculature and the ductal differentiation of the mammary epithelium. Moreover, there is emerging evidence for the involvement of NRG signals in the development and function of several other organ systems, and in human disease, including breast cancer and schizophrenia. Many different isoforms of the Neuregulin-1 gene are synthesized. Such isoforms differ in their tissue-specific expression patterns and their biological activities, thereby contributing to the great diversity of the in vivo functions of NRG1. Neuregulins transmit their signals to target cells by interacting with transmembrane tyrosine kinase receptors of the ErbB family. This family includes four members, the epidermal growth factor receptor (EGF-R, ErbB1, ErbB2, ErbB3, and ErbB4). Receptor-ligand interaction induces the heterodimerization of receptor monomers, which in turn results in the activation of intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. In vivo, functional NRG1 receptors are heterodimers composed of ErbB2 with either an ErbB3, or ErbB4 molecule. The tissue-specific distribution of the different receptor types further contributes to the diversity and specificity of the biological functions of this signaling pathway. It is a typical feature of the Neuregulin-1/ErbB signaling pathway to control sequential steps during the development of a particular organ system. For example, this pathway functions in early precursor proliferation, maturation, as well as in the myelination of Schwann cells. The systematic analysis of genetic models that have been established by the help of conventional as well as conditional gene targeting strategies in mice was instrumental for the uncovering of the multitude of biological functions of this signaling system. In this review the basic biology of the Neuregulin-1/ErbB system and how it relates to the in vivo functions were discussed with special emphasis to transgenic techniques in mice.
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PMID:The neuregulin-I/ErbB signaling system in development and disease. 1743 14

Papers from a generation ago suggested that phenothiazines--in particular trifluorperazine (Stelazine) a medicinal approved by the FDA and still commonly used for schizophrenia--downregulate the epidermal growth factor receptor. As numerous cancers--e.g., colon cancer, breast cancer, pancreatic cancer and glioblastoma--are dependent on signaling via this receptor, we here suggest that phenothiazines such as trifluorperazine be considered for use in epidermal growth factor receptor associated cancers.
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PMID:Consideration of use of phenothiazines in particular trifluorperazine for epidermal growth factor receptor associated cancers. 1744 10

The study of the profile of gene expression in a cell or tissue at a particular moment gives an insight into the plans of the cell for protein synthesis. Recent technological advances make it possible to analyze the expression of the entire genome in a single experiment. These "gene expression assays" complement or replace previous assays which measured the gene expression of only one gene, or a select group of genes. Within this chapter we outline the development of the gene expression assay and provide examples of the wide range of disciplines in which it is used. An overview of the current technologies is given, and includes an introduction to laser capture microdissection and linear amplification of RNA, both of which have extended the application of gene expression assays. Illustrative examples in the field of cancer and neuroscience highlight the scientific achievements. This technology has made in understanding the pathogenesis of diseases, including breast cancer, Huntington's disease, and schizophrenia. With recent advances including exon arrays to investigate alternative splicing, tiling arrays to investigate novel transcription start sites, and on-chip chromatin immunoprecipitation to investigate DNA-protein interactions, the future of gene expression assays is set to further our understanding of the complexities of gene expression.
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PMID:Gene expression assays. 1768 45

A disturbed methylation has been proposed as a mechanism via which homocysteine is associated with diseases like vascular disease, neural tube defects and mental disorders. Catechol-O-methyltransferase (COMT) is involved in the S-adenosylmethionine-dependent methylation of catecholamines and catecholestrogens and in this way contributes to homocysteine synthesis. COMT dysfunction has been related to schizophrenia and breast cancer. We hypothesized that COMT dysfunction by virtue of functional genetic polymorphisms may affect plasma total homocysteine (tHcy). Our primary objective was to study the association between common COMT polymorphisms and tHcy. Secondly, we evaluated these polymorphisms as a risk factor for recurrent venous thrombosis. We obtained genotype data from four polymorphisms in the COMT gene (rs2097603, rs4633, rs4680 [324G>A] and rs174699) from 401 population-based controls. We performed haplotype analysis to investigate the association between common haplotypes and tHcy. In addition, we assessed the rs4680 variant as a genetic risk factor in a case-control study on recurrent venous thrombosis (n = 169). We identified a common haplotype that was significantly associated with tHcy levels. This effect was largely explained by the rs4680 variant, resulting in an increase in tHcy of 10.4% (95% CI 0.01 to 0.21, p = 0.03) for 324AA compared with 324GG subjects. Interestingly, we found that the 324AA genotype was more common in venous thrombosis patients (OR 1.61 [95% CI 0.97 to 2.65], p = 0.06) compared to control subjects. We show that the COMT rs4680 variant modulates tHcy, and might be associated with venous thrombosis risk as well.
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PMID:Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk. 1806 18

The prioritization of genes within a candidate genomic region is an important step in the identification of causal gene variants affecting complex traits. Surprisingly, there have been very few reports of bioinformatics tools to perform such prioritization. The purpose of this article is to investigate the performance of 3 positional candidate gene software tools available, PosMed, GeneSniffer and SUSPECTS. The comparison was made for 40, 20 and 10 Mb regions in the human genome centred around known susceptibility genes for the common diseases breast cancer, Crohn's disease, age-related macular degeneration and schizophrenia. The known susceptibility gene was not always ranked highly, or not ranked at all, by 1 or more of the software tools. There was a large variation between the 3 tools regarding which genes were prioritized, and their rank order. PosMed and GeneSniffer were most similar in their prioritization gene list, whereas SUSPECTS identified the same candidate genes only for the narrowest (10 Mb) regions. Combining 2 or all of the candidate gene finding tools was superior in terms of ranking positional candidates. It is possible to reduce the number of candidate genes from a starting set in a region of interest by combining a variety of candidate gene finding tools. Conversely, we recommend caution in relying solely on single positional candidate gene prioritization tools. Our results confirm the obvious, that is, that starting with a narrower positional region gives a higher likelihood that the true susceptibility gene is selected, and that it is ranked highly. A narrow confidence interval for the mapping of complex trait genes by linkage can be achieved by maximizing marker informativeness and by having large samples. Our results suggest that the best approach to classify a minimum set of candidate genes is to take those genes that are prioritized by multiple prioritization tools.
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PMID:Prioritization of positional candidate genes using multiple web-based software tools. 1817 99

This paper explores chronologically the evolution of raised prolactin levels as an entity in psychiatric patients. Menstrual problems were described in patients with schizophrenia prior to the introduction of antipsychotic medication, but galactorrhoea and gynaecomastia were not commonly seen until the advent of antipsychotics. Following the introduction of antipsychotic medication single case reports of patients with galactorrhoea and gynaecomastia appeared. These were followed by a collection of case reports and the process reached today's data of laboratory defined rates of prolactin and sexual side effects. The paper also reviews the emerging research linking hyperprolactinaemia with increased risk of osteoporosis and possibly breast cancer. An overarching thread which runs throughout these publications, is the paucity of clinical research, which has only recently begun to be addressed.
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PMID:The evolution of hyperprolactinaemia as an entity in psychiatric patients. 1847 16

Most of the population receive their nutritional vitamin D requirements through exposure to solar ultraviolet (UV) radiation, with cutaneous synthesis estimated to provide 80-100% of the vitamin D requirements of the body. However, little is understood about the basic interaction of sunlight (UV) exposure and the subsequent photobiology and photochemistry of vitamin D production in humans. Low vitamin D (blood serum 25[OH]D) status has been linked to the development of a surprisingly wide range of diseases. Epidemiological data and animal studies indicate that low vitamin D is linked to rickets, bone mass loss, multiple sclerosis, hypertension, breast cancer, prostate cancer, colorectal cancer, insulin dependent diabetes and schizophrenia. Importantly some this emerging research associates such diseases with location and subsequent ultraviolet radiation exposures. This paper overviews concepts important to consider when assessing the impact of location and UV exposure on vitamin D synthesis.
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PMID:Geographic location and vitamin D synthesis. 1878 59

Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor alpha-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However, the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P-glycoprotein in cancer cells. In this study, we have investigated the effect of chlorpromazine on tamoxifen response of human breast cancer cells. We found that chlorpromazine worked synergistically together with tamoxifen with respect to reduction of cell growth and metabolic activity, both in the antiestrogen-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen, suggesting that chlorpromazine enhances the effect of tamoxifen through an estrogen receptor-mediated mechanism. To investigate this putative mechanism, we applied biophysical techniques to simple model membranes in the form of unilamellar liposomes of well-defined composition and found that chlorpromazine interacts strongly with lipid bilayers of different composition leading to increased permeability. This implies that chlorpromazine can change influx properties of membranes hence suggesting that chlorpromazine may be a promising chemosensitizing compound for enhancing the cytotoxic effect of tamoxifen.
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PMID:The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells. 1958 8


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