Lysophosphatidic acid (LPA) is a lipid mediator that may play an important role in growth and survival of carcinomas. In this study, LPA production and response were characterized in two human prostate cancer (CaP) cell lines: PC-3 and Du145. Bombesin, a neuroendocrine peptide that is mitogenic for CaP cells, stimulated focal adhesion kinase phosphorylation and activated the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Similar responses were elicited by 18:1 LPA (oleoyl-LPA). Studies using radioisotopic labeling revealed that both PC-3 and Du145 generate LPA and that LPA production is increased by bombesin. The kinetics of bombesin-induced phospholipase D activation and LPA production were similar. Using electrospray ionization mass spectrometry, 18:1 LPA was found to be an abundant LPA species in CaP cell medium. Structure activity studies of acyl-LPAs revealed that 18:1 LPA is most efficacious for activation of extracellular signal-regulated kinase and phospholipase D in CaP cells. Incubation with 18:1 LPA caused homologous desensitization of LPA response, whereas bombesin caused heterologous desensitization. LPA was present at nanomolar levels in medium from bombesin-treated cells. LPA extracted from the medium induced calcium mobilization in CaP cells. These results demonstrate that bioactive LPA is generated by CaP cells in response to a mitogen and suggest that 18:1 LPA can act as an autocrine mediator.
Parent training via videoconferencing may be an important tool for addressing ADHD in geographic locations that do not have access to appropriate treatment providers.
The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 confers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are unchanged in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt; inactive PLD2 has no effect. Expression of active PLD2 is associated with increased spreading and elongation of cells on tissue culture plastic, whereas inactive PLD2 inhibits cell spreading. Inactive PLD2 also inhibits cell adhesion, migration, and serum-induced invasion. Cells expressing active PLD2 form metastases in syngeneic mice, as do the parental cells; cells expressing inactive PLD2 form fewer metastases than parental cells. In summary, active PLD2 enhances FAK phosphorylation, Akt activation, and cell invasion in EL4 lymphoma cells, whereas inactive PLD2 exerts inhibitory effects on adhesion, migration, invasion, and tumor formation. Overall, expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis.
BackgroundThe evidence for effectiveness of Cognitive Behaviour Therapy (CBT) is robust and the national organizations in the United Kingdom and the United States recommend its use. It is not utilized to its full potential in low and middle-income countries. Adaptation of CBT treatment to the target culture may facilitate its uptake.This study explored views of patients with schizophrenia, their caregivers, and mental health professionals for the purpose of cultural adaptation of CBT.MethodThe project was conducted in a teaching hospital in China. Systematic content and question analysis were the techniques we used to analyse the data generated in a series of qualitative interviews (N 45) in China. After identification of emerging themes and categories we compared and contrasted the themes across different interviews recursively. Triangulation of themes and concepts was undertaken to compare further and contrast the data from the different participating groups.ResultsThis work highlighted the barriers in therapy as well as opportunities for use of CBT in that environment. Patients and their carers in China use a bio-psycho-spiritual-social model of illness. CBT is not commonly used to help those with schizophrenia in China.ConclusionsThis study will facilitate the therapists using CBT for people with psychosis in China. These results require to be tested in clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-017-1290-6) contains supplementary material, which is available to authorized users.
Spinocerebellar ataxia type 3 (SCA3) is caused by an abnormal expansion of the cytosine-adenine-guanine (CAG) triplet in ATXN3, which translates into a polyglutamine (polyQ) tract within ataxin-3 (ATXN3) protein. Although the pathogenic mechanisms remain unclear, it is well established that expression of mutant forms of ATXN3 carrying an expanded polyQ domain are involved in SCA3 pathogenesis, and several strategies to suppress mutant ATXN3 have shown promising potential for SCA3 treatment. In this study, we described successful clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of the expanded polyQ-encoding region of ATXN3 in induced pluripotent stem cells (iPSCs) derived from a SCA3 patient, and these patient-specific iPSCs retained pluripotency and neural differentiation following expanded polyQ deletion. Furthermore, the ubiquitin-binding capacity of ATXN3 was retained in the neural cells differentiated from the corrected iPSCs. For the first time, this work provides preliminary data for gene editing by CRISPR/Cas9 in SCA3, and demonstrates the feasibility of using a single-guide RNA pair to delete the expanded polyQ-encoding region of ATXN3, suggesting the potential efficacy of this method for future therapeutic application.
The present study suggested that coffee intake was associated with an increased risk of lung cancer.
Asian Pac J Cancer Prev, 15 (16), 6535-6541 IntroductionBreast cancer related lymphedema (BCRL)is a chronic and common complication caused by abnormal accumulation of protein-rich fluid in the interstitial space secondary to inadequate lymphatic drainage, which manifests unilateral or bilateral upper extremity swelling in the clinical. (Cheville et al., 2003). Lymphedema and its related symptoms (pain, heaviness, tightness, and decreased range of motion) seriously affect recreational and social relationships (Hayes et al., 2012). Patients with BCRL have a lower quality of life, a higher level of anxiety or depression (Pyszel et al., 2006;Heiney et al., 2007).Due to differences in study designs, measurement methods and criterias , length of follow-up, lymphedema definitions and timing of lymphedema measurement since diagnosis and treatment, previous studies have shown about 20% of breast cancer survivors will develop lymphedema. (sakorafas et al., 2006) In recent years, many studies have established risk factors of BCRL, but conclusions are not consistent, which even contradict each other from some studies. The study systematically reviews the risk factors for BCRL with meta-analysis method to increase the credibility of the conclusions for the purpose of providing scientific evidence for early prevention of lymphedema in clinical work. Materials and Methods Literature SearchWe searched comprehensively clinical studies which were published in PubMed, Ovid, EMbase, the Cochrane Library from January 1, 1996 to December 30, 2012. The MeSH headings and keywords in this search used included "breast cancer", "upper extremity", "lymphedema" and "risk factors" Relevant articles were identified and their references were checked for additional studies.The search strategy used: ( ("Breast Neoplasms" (Mesh) AND "Upper Extremity" (Mesh)) AND ("Lymphedema" (Mesh) OR "Edema" (Mesh)) AND ("1996/01/01" (PDAT) : "2012/12/31" (PDAT)) Inclusion and Exclusion CriteriaInclusion criteria: studies of female patients with unilateral breast cancer; the primary studies of risk factors for BCRL published abroad.Exclusion criteria: studies of patients with bilateral breast cancer, primary lymphoedema, or metastatic disease (n=258); review, meta-analyses, editorial, comment , and case reports (n=121); studies that did not either inform OR and 95%CI or provide adequate information to calculate the OR and its variance (n=39); non-English-language studies (n=8).
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