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1.
Compr Psychiatry ; 103: 152197, 2020 11.
Article in English | MEDLINE | ID: mdl-32992073

ABSTRACT

BACKGROUND: Social media holds exciting promise for advancing mental health research recruitment, however, the extent and efficacy to which these platforms are currently in use are underexplored. OBJECTIVE: A systematic review was conducted to characterize the current use and efficacy of social media in recruiting participants for mental health research. METHOD: A literature review was performed using MEDLINE, EMBASE, and PsychINFO. Only non-duplicative manuscripts written in the English language and published between 1/1/2004-3/31/2019 were selected for further screening. Data extracted included study type and design, participant inclusion criteria, social media platform, advertising strategy, final recruited sample size, recruitment location, year, monetary incentives, comparison to other recruitment methods if performed, and final cost per participant. RESULTS: A total of 176 unique studies that used social media for mental health research recruitment were reviewed. The majority of studies were cross-sectional (62.5%) in design and recruited adults. Facebook was overwhelmingly the recruitment platform of choice (92.6%), with the use of paid advertisements being the predominant strategy (60.8%). Of the reviewed studies, substance abuse (43.8%) and mood disorders (15.3%) were the primary subjects of investigation. In 68.3% of studies, social media recruitment performed as well as or better than traditional recruitment methods in the number and cost of final enrolled participants. The majority of studies used Facebook for recruitment at a median cost per final recruited study participant of $19.47. In 55.6% of the studies, social media recruitment was the more cost-effective recruitment method when compared to traditional methods (e.g., referrals, mailing). CONCLUSION: Social media appears to be an effective and economical recruitment tool for mental health research. The platform raises methodological and privacy concerns not covered in current research regulations that warrant additional consideration.


Subject(s)
Mental Health , Social Media , Adult , Advertising , Cross-Sectional Studies , Humans , Research Design
2.
Cogn Dev ; 49: 105-115, 2019.
Article in English | MEDLINE | ID: mdl-31105381

ABSTRACT

For the initiated, college may be remembered as a care-free and playful time. However, for contemporary college students the transition to college is challenging with only 1 in 3 returning for their second year of study, and the challenges are even greater for first-generation and low-income students. The interactive digital platform of the current study invited low-income first-year students to write about and reflect upon their transition to college. It was through the higher order cognitive process of writing, which involved deciding which words, symbols, and punctuation to use to express a particular thought to a particular audience, that the students made-sense of their experiences. Our analyses detail how students integrated new approaches for communicating their thoughts in writing and how these techniques changed over time. We show how first-year students used the affordances of the keyboard and an interactive blog to create a reflective and supportive digital writing style somewhere between the formality of the college essay and the freewheeling social media post. The emerging playful style was marked by the introduction of computer-mediated communication (CMC) cues typical of social media platforms like Twitter and Facebook, including emoticons and emojis, hashtags, repeated capital letters, repeated punctuation, and abbreviations such as lol, to the college course context. A path analysis of 209 blog posts and 161 comments over four time points, coupled with a qualitative case study showed that students developed their use of CMC cues first on the social level through comments and later on the individual level in their posts. Our analyses show how students integrated CMC cues to communicate humor and critique as they created a new genre of college writing. The social support and the CMC cues were concretely relevant to the students' development of knowledge and practice of what it meant to write in college and what it meant to become a college student.

3.
Rev Med Chil ; 147(9): 1159-1166, 2019 Sep.
Article in Spanish | MEDLINE | ID: mdl-33625450

ABSTRACT

In 2017, migrants were 4.35% of the Chilean population, mainly from Peru and Colombia. From 2015, the amount of migrants from Central America, particularly from Haiti increased notably. This process changed the phenotype of the male population, increasing the proportion of black men, mainly between 20 and 50 years. Afro-descendant men have a higher risk for prostate cancer, and the tumor can appear as early as 40 years of age among them. This increase will have future repercussions on the public health system, since part of these men have low income and poor living conditions. Therefore, it is necessary to discuss early detection strategies focused on this population, including education for both patients and health professionals. This review includes data on the reality of migration in Chile and its impact on the health system. The higher incidence and mortality of prostate cancer in the migrant population is reviewed and risk-adjusted screening strategies are proposed.


Subject(s)
Emigrants and Immigrants , Prostatic Neoplasms , Black or African American , Chile/epidemiology , Colombia , Haiti , Humans , Male , Peru/epidemiology
4.
J Endourol ; 38(3): 212-218, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38185914

ABSTRACT

Introduction and objective: Magnetic-assisted robotic surgery (MARS) has been developed to maximize patient benefits of minimally invasive surgery while enhancing surgeon control and visualization. MARS platform (Levita Magnetics) comprises two robotic arms that provide control to an external magnetic controller and an off-the-shelf laparoscopic camera. Our aim was to evaluate the safety and efficacy of the MARS platform in laparoscopic renal and adrenal procedure for the first time. Methods: This is a prospective, single-arm, open-label study (Clinical Trials Identifier: NCT05353777) including patients with renal or adrenal pathology analysis, submitted to laparoscopic procedure between April and June 2022. Patients were followed up to 30 days postoperatively. Preoperative, intraoperative, and postoperative data were recorded. Polynomial regression was used to determine the learning curve for docking time. Results: Fifteen cases were performed using the MARS platform (three partial nephrectomies, five total nephrectomies for benign pathology analysis, four radical nephrectomies, and three adrenalectomies) corresponding to 10 women and 5 men (mean age, 55 years [18-77]; average body mass index, 29 cm/m2 [22-39]). No cases required conversion to open procedure and all patients were discharged on the first or second postoperative day. No complications or re-admissions were reported within the first 30 days. All oncologic cases had negative margins. Learning curve was achieved by the fourth case, diminishing docking time from 5.22 (2.6-11.5) to 2.68 minutes (2.1-3.8) (p = 0.002). The learning curve was fitted to a cubic regression (R2 = 0.714). Conclusion: This is the first clinical study demonstrating the safety and versatility of the MARS platform in urologic procedures. The robot was especially useful for tissue retraction, avoiding additional incisions and the need for a surgical assistant while increasing surgeon control and visualization. The learning curve was rapid, achieving a short docking time. MARS is a promising new technology that could be successfully evaluated in other surgeries.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Robotics , Urology , Female , Humans , Male , Middle Aged , Laparoscopy/methods , Magnetic Phenomena , Nephrectomy/methods , Prospective Studies , Robotic Surgical Procedures/methods
5.
J Endourol ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38874940

ABSTRACT

This research presents our application of artificial intelligence (AI) in predicting urolithiasis risk. Previous applications, including AI for stone disease, have focused on stone composition and aiding diagnostic imaging. AI applications centered around patient-specific characteristics, lifestyle considerations, and diet have been limited. Our study comprised a robust sample size of 976 Chilean participants, with meticulously analyzed demographic, lifestyle, and health data through a comprehensive questionnaire. We developed a predictive model using various classifiers, including logistic regression, decision trees, random forests, and extra trees, reaching high accuracy (88%) in identifying individuals at risk of kidney stone formation. Key protective factors highlighted by the algorithm include the pivotal role of hydration, physical activity, and dietary patterns that played a crucial role, emphasizing the protective nature of higher fruit and vegetable intake, balanced dairy consumption, and the nuanced impact of specific protein sources on kidney stone risk. In contrast, identified risk factors encompassed gender disparities with males found to be 2.31 times more likely to develop kidney stones than females. Thirst and self-perceived dark urine color emerged as strong predictors, with a significant increase in the likelihood of stone formation. The development of predictive tools with AI, in urolithiasis management signifies a paradigm shift toward more precise and personalized health care. The algorithm's ability to process extensive datasets, including dietary habits, heralds a new era of data-driven medical practice. This research underscores the transformative impact of AI in medical diagnostics and prevention, paving the way for a future where health care interventions are not only more effective but also tailored to individual patient needs. In this case, AI is an important tool that can help patients stay healthy, prevent diseases, and make informed decisions about their overall well-being.

6.
J Psychiatr Res ; 176: 58-67, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38843580

ABSTRACT

OBJECTIVE: The Buried in Treasures (BIT) workshop is a promising treatment for hoarding disorder (HD), though many participants struggle with home uncluttering. This randomized waitlist-controlled trial investigated the efficacy of a version of BIT, augmented with in-home uncluttering practice (BIT+). METHOD: Adults (N = 41) with hoarding disorder were recruited from the community and randomly assigned to BIT+ or waitlist. BIT+ consisted of 16 sessions of the BIT workshop and 10 uncluttering home visits over 18 weeks. Outcome measures included the Saving Inventory-Revised (self-report) and the Clutter Image Rating Scale (self and independent evaluator rated). Between group repeated measures analyses using general linear modeling examined the effect of BIT+ vs waitlist control on hoarding symptoms after 18 weeks. Within group analyses examined pre-post effects for all BIT+ participants combined after 18 weeks. RESULTS: After 18 weeks, BIT+ participants benefited significantly more than waitlist controls on hoarding severity with large effect size (Cohen's d = 1.5, p < .001). BIT+ was also associated with improvement reductions in hoarding symptoms, clutter, and functional impairment. CONCLUSIONS: The BIT+ intervention offers promise as a treatment option for hoarding. Adding in-home uncluttering practice may incrementally improve discarding practices. Future controlled trials are warranted.

7.
J Cancer Res Clin Oncol ; 149(8): 4701-4717, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36222898

ABSTRACT

PURPOSE: Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as markers for disease initiation, progression, and response to treatment. This under-utilised tool provides insights into a better understanding of prostate cancer. METHODS: EV from serum and urine of healthy men and castration-resistant prostate cancer (CRPC) patients were isolated and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC-MS) analyses were conducted. RESULTS: There was a successful enrichment of small EV/exosomes isolated from serum and urine. EV derived from biological fluids of CRPC patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine samples from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient. CONCLUSION: Some of the EV proteins identified from our analyses have potential to be used as CRPC markers. These markers may depict a pattern in cancer progression through non-invasive sample collection.


Subject(s)
Body Fluids , Exosomes , Extracellular Vesicles , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Proteomics , Extracellular Vesicles/metabolism
8.
Anticancer Drugs ; 23(9): 959-69, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22713594

ABSTRACT

Gonadotropin-releasing hormone (GnRH) agonists are widely used for the treatment of advanced prostate cancer (PCa). Agonists activate the GnRH receptor (GnRH-R), triggering apoptosis in PCa cells. In gonadotropes, the amount of GnRH-R in the plasma membrane is regulated by protein folding and endoplasmic reticulum retention, mechanisms that can be overcome by the pharmacoperone IN3. Our aim was to describe the intracellular distribution of GnRH-R in PCa cells and its relation to response to GnRH analog treatments. The expressions of GnRH-R in PCa biopsies were evaluated by immunohistochemistry and the intracellular distribution was determined by immunofluorescence in primary cell cultures from human PCa samples. Cultured cells were pretreated with IN3 and then with leuprolide. Cell survival was evaluated by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) thiazolyl blue formazan and cell cycle and apoptosis by flow cytometry. We observed that the expression of GnRH-R decreased according to malignant progression. Most GnRH-R are located inside the cell, colocalizing with endoplasmic reticulum markers. The treatment with IN3 decreased cellular GnRH-R retention, increasing plasma membrane expression in approximately 60%. Pretreatment with IN3 decreased PCa cell survival compared with leuprolide-alone treatment, primarily because of an increase in apoptosis. We conclude that the response of PCa cells to leuprolide is related to the amount of GnRH-R in the plasma membrane. Therefore, pretreatment evaluation of the amount of these receptors may be a predictor of the outcome of leuprolide treatment in PCa patients. Assessment of systemic IN3 effect would be necessary to determine its utility as an adjuvant treatment in hormone-resistant tumors.


Subject(s)
Apoptosis/drug effects , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cell Membrane/drug effects , Indoles/pharmacology , Leuprolide/pharmacology , Prostatic Neoplasms/pathology , Pyridines/pharmacology , Receptors, LHRH/agonists , Blotting, Western , Cell Culture Techniques , Cell Cycle/drug effects , Cell Membrane/metabolism , Cell Survival/drug effects , Drug Synergism , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Flow Cytometry , Humans , Immunohistochemistry , Male , Prostatic Neoplasms/metabolism , Protein Folding , Receptors, LHRH/biosynthesis , Tumor Cells, Cultured
9.
Sci Rep ; 12(1): 21752, 2022 12 16.
Article in English | MEDLINE | ID: mdl-36526652

ABSTRACT

Insight impairment contributes significantly to morbidity in psychiatric disorders. The neurologic concept of anosognosia, reflecting deficits in metacognitive awareness of illness, is increasingly understood as relevant to psychopathology, but has been little explored in psychiatric disorders other than schizophrenia. We explored anosognosia as an aspect of insight impairment in n = 71 individuals with DSM-5 hoarding disorder. We used a standardized clutter severity measure to assess whether individuals with hoarding disorder underreport home clutter levels relative to independent examiners. We then explored whether underreporting, as a proxy for anosognosia, is predicted by clinical or neurocognitive behavioral measures. We found that individuals with hoarding disorder underreport their clutter, and that underreporting is predicted by objective severity of clutter. In an n = 53 subset of participants, we found that underreporting is predicted by altered performance on tests of cognitive control and inhibition, specifically Go/No-Go and Stroop tests. The relation of underreporting to objective clutter, the cardinal symptom of hoarding disorder, suggests that anosognosia may reflect core pathophysiology of the disorder. The neurocognitive predictors of clutter underreporting suggest that anosognosia in hoarding disorder shares a neural basis with metacognitive awareness deficits in other neuropsychiatric disorders and that executive anosognosia may be a transdiagnostic manifestation of psychopathology.


Subject(s)
Agnosia , Hoarding Disorder , Metacognition , Humans , Hoarding Disorder/psychology , Agnosia/diagnosis , Diagnostic and Statistical Manual of Mental Disorders
10.
Prostate ; 71(16): 1810-7, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21480311

ABSTRACT

BACKGROUND: In several cancer types, expression of multidrug resistance (MDR) proteins has been associated with lack of chemotherapy response. In advanced prostate cancer (PCa) the use of chemotherapy is mainly palliative due to its high resistance. Previously, we described that MDR phenotype in PCa could be related with high basal and drug-induced expression of MDR proteins P-Glycoprotein (P-Gp), MRP1, and LRP. METHODS: Using primary cell cultures from PCa patients, we evaluated the effect of function and expression inhibition of P-Gp, MRP1, and LRP, on cell survival after chemotherapy exposure. Cells were treated with specific MDR protein substrates (docetaxel and mitoxantrone for P-Gp, methotrexate for MRP1 and cisplatin for LRP) and pharmacological inhibitors (cyclosporine A, genistein and 3-aminobenzamide), and cell survival was evaluated trough 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell cycle analysis. MRP1 activity was evaluated by FACS using the specific inhibitor MK571. Cells were transfected with MDR proteins siRNAs and treated with the corresponding substrates. RESULTS: PCa cell resistance to MDR protein substrates was partially reversed, decreasing cell survival in around 20%, by treating primary cell cultures with specific pharmacological inhibitors. PCa cells transfected with siRNAs against MDR proteins decreased cell survival when treated with the corresponding drugs. Docetaxel was the most effective chemotherapeutic drug to induce cell death and decrease survival. CONCLUSION: Low chemotherapy response in PCa could be explained, in part, by over-expression of functional MDR proteins. Expression and function of these proteins should be evaluated to enhance efficacy of docetaxel-based therapies of patients with hormone-resistant PCa.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Drug Resistance, Neoplasm/genetics , Multidrug Resistance-Associated Proteins/genetics , Prostatic Neoplasms/drug therapy , RNA, Small Interfering/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Apoptosis/drug effects , Apoptosis/physiology , Cell Survival/drug effects , Cell Survival/physiology , Combined Modality Therapy , Humans , Male , Phenotype , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Tumor Cells, Cultured , Vault Ribonucleoprotein Particles/genetics
11.
Int J Radiat Biol ; 97(11): 1555-1562, 2021.
Article in English | MEDLINE | ID: mdl-34519609

ABSTRACT

BACKGROUND: GnRH analogs are widely used as neoadjuvant agents for radiotherapy in prostate cancer (PCa) patients, with well-documented effects in reducing tumor bulk and increasing progression-free survival. GnRH analogs act locally in the prostate by triggering apoptosis of PCa cells via activation of the GnRH receptor (GnRHR). During PCa progression, the distribution of GnRHR within the cell is altered, with reduced expression in the cell membrane and remaining sequestered in the endoplasmic reticulum. Pharmacoperone IN3 is able to relocalize GnRHR to the cell membrane. The aim of this study was to evaluate the effect of radiation on PCa cells pretreated with leuprolide, alone or in combination with IN3, as radiosensitizers. MATERIAL AND METHODS: PC3 and human PCa primary cell cultures were treated with IN3 for 24 h, followed by different doses of leuprolide for 48 h and, finally, single doses of radiation (3, 6, and 9 Gy). After radiation, cell survival, apoptosis, cell cycle distribution, and colony growth were evaluated. RESULTS: Radiation reduced cell survival and increased apoptosis in a dose-dependent manner. This effect was also directly related to leuprolide concentration. Pretreatment with IN3 enhanced apoptosis and decreased cell survival, also observing a higher proportion of cells arrested in G2. CONCLUSION: Neoadjuvant leuprolide increases radiation-mediated apoptosis of PCa cells. This effect was enhanced by pretreatment with pharmacoperone IN3. Clinical use of IN3 as a radiosensitizer combined with androgen deprivation therapy to improve survival of patients with PCa remains to be evaluated.


Subject(s)
Prostatic Neoplasms , Androgen Antagonists , Gonadotropin-Releasing Hormone , Humans , Leuprolide/pharmacology , Male , Prostate , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Radiation-Sensitizing Agents/pharmacology , Receptors, LHRH
12.
J Psychiatr Res ; 137: 597-602, 2021 05.
Article in English | MEDLINE | ID: mdl-33309063

ABSTRACT

Hoarding disorder (HD), characterized by difficulty parting with possessions and functionally impairing clutter, affects 2-6% of the population. Originally considered part of Obsessive-Compulsive Disorder (OCD), HD became a distinct diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. While sleep impacts OCD, little is known about sleep in HD. As HD patients often report poor sleep in clinical settings, understanding global subjective sleep quality and disturbances may lead to novel therapeutic targets. To address this gap, the authors used a sample of convenience: an existing data set designed to screen research study eligibility and explore the psychopathology and phenomenology of OCD and HD. The data set included information collected from individuals with HD (n = 38), OCD (n = 26), and healthy participants (n = 22) about insomnia, sleep quality, and mood using interviews and structured instruments including the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Depression Anxiety Stress Scales (DASS). In this data set, HD and OCD groups reported significantly greater insomnia symptoms and poorer sleep quality compared with healthy controls while controlling for depression, age, and gender. A sizable minority of HD and OCD individuals met criteria for comorbid sleep disorders. OCD and HD groups differed in delayed sleep phase prevalence. To our knowledge, this is the first study examining subjective sleep quality and insomnia in HD as compared to healthy individuals and those with OCD, while controlling for relevant clinical characteristics. Given that there are evidence-based treatments for insomnia and other sleep disorders, our study raises the possibility that treatment interventions targeting sleep may improve HD outcomes.


Subject(s)
Hoarding Disorder , Hoarding , Obsessive-Compulsive Disorder , Adult , Diagnostic and Statistical Manual of Mental Disorders , Hoarding Disorder/epidemiology , Humans , Obsessive-Compulsive Disorder/complications , Obsessive-Compulsive Disorder/epidemiology , Prevalence , Sleep
13.
J Psychiatr Res ; 140: 357-363, 2021 08.
Article in English | MEDLINE | ID: mdl-34139458

ABSTRACT

INTRODUCTION: Obsessive-compulsive disorder (OCD), characterized by repetitive anxiety-inducing intrusive thoughts and compulsive behaviors, is associated with higher suicide ideation and suicide attempts than the general population. This study investigates the prevalence and the correlates of current suicide risk in adult outpatients in an international multisite cross-sectional sample of OCD outpatients. METHODS: Data were derived from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network's cross-sectional data set (N = 409). Current suicide risk (assessed by Item C of the MINI) and diagnoses of psychiatric disorders were based on DSM-IV. Chi-squared test for categorical variables and t-test for continuous variables were used to make statistical inferences about main features associated with current suicide risk. P < .05 was considered as statistically significant. RESULTS: The prevalence of current suicidal risk was 15.9%, with equal likelihood in sociodemographic variables, including age and gender. Increased rates of major depression and generalized anxiety disorder were associated to higher current suicide risk. Current suicide risk was also associated with higher severity of OCD, depressive comorbidity, and higher levels of disability. There were no significant differences in treatment correlates-including type of treatment and psychiatric hospitalizations-between the groups of individuals with and without current suicide risk. CONCLUSION: Our findings suggest that current suicide risk is common in patients with OCD and associated with various forms of pathology. Our work also provides further empirical data to support what is already known clinically: a worse clinical picture characterized by a high severity of OCD, high distress related to obsessions and compulsions, and the presence of comorbidities such as major depression and generalized anxiety disorder should be considered as relevant risk factors for suicide risk.


Subject(s)
Obsessive-Compulsive Disorder , Adult , Comorbidity , Compulsive Personality Disorder , Cross-Sectional Studies , Humans , Obsessive-Compulsive Disorder/epidemiology , Prevalence , Suicide, Attempted
14.
J Extracell Vesicles ; 10(7): e12093, 2021 05.
Article in English | MEDLINE | ID: mdl-34035881

ABSTRACT

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.


Subject(s)
Biomarkers/urine , Extracellular Vesicles/physiology , Urinary Tract/pathology , Advisory Committees , Body Fluids/metabolism , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Humans , Kidney , Reference Standards , Reproducibility of Results , Societies , Urine
15.
Prostate ; 69(10): 1025-33, 2009 Jul 01.
Article in English | MEDLINE | ID: mdl-19301301

ABSTRACT

BACKGROUND: Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic-pituitary-gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH-mediated apoptosis on prostate cancer cells were studied. METHODS: Primary cultures from PCa and benign prostatic hyperplasia (BPH) (non-malignant control) were derived from samples provided by our Institutional Hospital. Cell cultures were incubated for 24 hr with 20 ng/ml of GnRH agonist Leuprolide (Lp) or antagonist Cetrorelix (Cx). Apoptosis was evaluated by studying the expression of Bax and Bcl-2 and the activation of caspase-9 (intrinsic pathway), caspase-8 (extrinsic pathway), and caspase-3. Also, mRNA level, protein expression and phosphorylation of p53 were studied. RESULTS: Cleaved caspase-8 and -3, but not -9, increased in presence of Lp and Cx in PCa cell cultures. Bax and Bcl-2 mRNA levels showed no changes after GnRH-analog treatments. Only Bax protein showed an increase after Cx treatment in PCa cell cultures. p53 mRNA level was higher in PCa than in BPH cell cultures. Lp and Cx increased p53 expression and phosphorylation in PCa cell cultures. CONCLUSIONS: Apoptosis induced by GnRH analogs seems to be mediated by extrinsic pathway involving p53 phosphorylation. Phosphorylated-p53 might be associated with the increase in apoptotic NGF receptor, p75, previously reported by our laboratory. These findings reinforce the concept of clinical use of GnRH analogs for PCa suggesting that intraprostatic treatment may be more effective.


Subject(s)
Adenocarcinoma/drug therapy , Apoptosis/physiology , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/pharmacology , Prostatic Neoplasms/drug therapy , Signal Transduction/physiology , Tumor Suppressor Protein p53/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Apoptosis/drug effects , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Male , Phosphorylation/drug effects , Phosphorylation/physiology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Tumor Cells, Cultured , Tumor Suppressor Protein p53/physiology
16.
Prostate ; 69(13): 1448-59, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19496068

ABSTRACT

BACKGROUND: Multidrug resistance (MDR) proteins have been associated with the lack of chemotherapy response. Expression of these proteins has been described in the prostate, but there is no information about their role in the chemotherapy response of prostate cancer (PC). We studied the gene and protein expression of MDR proteins in primary cell cultures from PC tumors and PC cell lines, their relationship with chemotherapy and their effects on cell survival. METHODS: Primary cell cultures from PC were obtained from samples provided by our Institutional Hospital. Cell lines LNCaP, PC3, and DU145 were also examined. Cells were treated during 72 hr with several chemotherapeutic drugs. Protein and mRNA expressions of P-glycoprotein (P-Gp), MRP1 and LRP, before and after drug treatment, were evaluated by RT-PCR and Western blot analyses. The effect on cell survival was evaluated by proliferation assays (MTT), and cell cycle and apoptosis by flow cytometry. RESULTS: Primary PC cultures exhibited higher MDR protein expression and lower drug sensitivity than cell lines, in which P-Gp was not detected. Docetaxel and mitoxantrone displayed the highest apoptotic effect. Exposure to chemotherapeutic drugs increased apoptosis, cell cycle arrest, and MDR expression. Long-term treatment with doxorubicin diminished apoptosis elicited by all drugs examined in this study, suggesting a cross-resistance phenomenon. CONCLUSIONS: Low chemotherapy response observed in PC primary cultures could be explained, in part, by the high levels of MDR proteins (intrinsic MDR phenotype), and also, by their over-expression induced after long-term exposure to drugs (acquired MDR phenotype), which increase treatment resistance. Prostate 69: 1448-1459, 2009. (c) 2009 Wiley-Liss, Inc.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm/genetics , Multidrug Resistance-Associated Proteins/genetics , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/physiopathology , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Apoptosis/drug effects , Cell Survival/drug effects , Cisplatin/pharmacology , Docetaxel , Humans , Male , Methotrexate/pharmacology , Mitoxantrone/pharmacology , Prostatic Neoplasms/pathology , Taxoids/pharmacology , Tumor Cells, Cultured , Vault Ribonucleoprotein Particles/genetics
17.
Int J Androl ; 32(6): 607-15, 2009 Dec.
Article in English | MEDLINE | ID: mdl-18637152

ABSTRACT

7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP). We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion, proliferation and gene expression of primary cell cultures from human BPH and CaP. Moreover, the effect of these androgens was examined in the presence of finasteride to determine the influence of the 5-alpha reductase (5-AR) activity on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1, 10 and 100 nM of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen (PSA) was measured by micro particles immunoassay and proliferation rate by spectrophotometric assay (MTT) and by the immunochemical detection of the proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene) was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments increased PSA secretion and proliferation rate with a potency ranged between T and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The studies with finasteride showed that in BPH and CaP cells, the conversion of T into DHT significantly contributes to its effect on the proliferation and PSA secretion, and corroborated the resistance of MENT to the 5-AR. The effect of MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than DHT. It is concluded that MENT increases proliferative and secretory activities and gene expression on pathological prostate cells although in less extent than the active metabolite DHT. Furthermore, the fall of endogenous concentration of T during MENT treatment anticipates that this androgen will be of low impact for the prostate.


Subject(s)
Nandrolone/analogs & derivatives , Prostate/metabolism , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Androgens/metabolism , Androgens/therapeutic use , Dihydrotestosterone/metabolism , Dihydrotestosterone/pharmacology , Dihydrotestosterone/therapeutic use , Finasteride/metabolism , Finasteride/pharmacology , Finasteride/therapeutic use , Humans , Male , Nandrolone/metabolism , Nandrolone/therapeutic use , Prostate/pathology , Prostate-Specific Antigen/metabolism , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Reverse Transcriptase Polymerase Chain Reaction , Testosterone/metabolism , Testosterone/pharmacology , Testosterone/therapeutic use , Testosterone Congeners/metabolism , Testosterone Congeners/therapeutic use
18.
J Psychiatr Res ; 107: 145-150, 2018 12.
Article in English | MEDLINE | ID: mdl-30419524

ABSTRACT

Hoarding disorder is characterized by difficulty parting with possessions and by clutter that impairs the functionality of living spaces. Cognitive behavioral therapy conducted by a therapist (individual or in a group) for hoarding symptoms has shown promise. For those who cannot afford or access the services of a therapist, one alternative is an evidence-based, highly structured, short-term, skills-based group using CBT principles but led by non-professional facilitators (the Buried in Treasures [BIT] Workshop). BIT has achieved improvement rates similar to those of psychologist-led CBT. Regardless of modality, however, clinically relevant symptoms remain after treatment, and new approaches to augment existing treatments are needed. Based on two recent studies - one reporting that personalized care and accountability made treatments more acceptable to individuals with hoarding disorder and another reporting that greater number of home sessions were associated with better clinical outcomes, we tested the feasibility and effectiveness of adding personalized, in-home uncluttering sessions to the final weeks of BIT. Participants (n = 5) had 15 sessions of BIT and up to 20 hours of in-home uncluttering. Reductions in hoarding symptoms, clutter, and impairment of daily activities were observed. Treatment response rate was comparable to rates in other BIT studies, with continued improvement in clutter level after in-home uncluttering sessions. This small study suggests that adding in-home uncluttering sessions to BIT is feasible and effective.


Subject(s)
Hoarding Disorder/therapy , Outcome Assessment, Health Care , Psychotherapy, Group/methods , Activities of Daily Living , Adult , Aged , Feasibility Studies , Female , Humans , Middle Aged , Pilot Projects
19.
Oncotarget ; 7(4): 3993-4008, 2016 Jan 26.
Article in English | MEDLINE | ID: mdl-26675257

ABSTRACT

The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.


Subject(s)
Biomarkers, Tumor/genetics , Exosomes/genetics , Fibroblasts/metabolism , MicroRNAs/genetics , Neoplastic Stem Cells/metabolism , Prostate/metabolism , Prostatic Neoplasms/genetics , Apoptosis , Biomarkers, Tumor/metabolism , Blotting, Western , Cell Movement , Cell Proliferation , Computational Biology , Disease Progression , Fibroblasts/pathology , Gene Expression Regulation, Neoplastic , High-Throughput Nucleotide Sequencing , Humans , Male , Neoplastic Stem Cells/pathology , Prostate/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/secondary , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
20.
Rev. méd. Chile ; 147(9): 1159-1166, set. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058659

ABSTRACT

In 2017, migrants were 4.35% of the Chilean population, mainly from Peru and Colombia. From 2015, the amount of migrants from Central America, particularly from Haiti increased notably. This process changed the phenotype of the male population, increasing the proportion of black men, mainly between 20 and 50 years. Afro-descendant men have a higher risk for prostate cancer, and the tumor can appear as early as 40 years of age among them. This increase will have future repercussions on the public health system, since part of these men have low income and poor living conditions. Therefore, it is necessary to discuss early detection strategies focused on this population, including education for both patients and health professionals. This review includes data on the reality of migration in Chile and its impact on the health system. The higher incidence and mortality of prostate cancer in the migrant population is reviewed and risk-adjusted screening strategies are proposed.


Subject(s)
Humans , Male , Prostatic Neoplasms , Emigrants and Immigrants , Peru/epidemiology , Black or African American , Chile/epidemiology , Colombia , Haiti
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