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BACKGROUND: Cross-cultural psychosis research has mostly focused on outcomes, rather than patient and family experiences. Therefore, our aim was to examine differences in patients' and families' experiences of their treating teams in early intervention services for psychosis in Chennai, India [low- and middle-income country] and Montreal, Canada [high-income country]. METHODS: Patients (165 in Chennai, 128 in Montreal) and their families (135 in Chennai, 110 in Montreal) completed Show me you care, a patient- and family-reported experience measure, after Months 3, 12, and 24 in treatment. The measure assesses the extent to which patients and families view treating teams as being supportive. A linear mixed model with longitudinal data from patient and family dyads was used to test the effect of site (Chennai, Montreal), stakeholder (patient, family), and time on Show me you care scores. This was followed by separate linear mixed effect models for patients and families with age and gender, as well as symptom severity and functioning as time-varying covariates. RESULTS: As hypothesized, Chennai patients and families reported more supportive behaviours from their treating teams (ß=4.04; ß= 9, respectively) than did Montreal patients (Intercept =49.6) and families (Intercept=42.45). Higher symptom severity over follow-up was associated with patients reporting lower supportive behaviours from treating teams. Higher levels of positive symptoms (but lower levels of negative symptoms) over follow-up were associated with families reporting lower supportive behaviours from treating teams. There was no effect of time, age, gender and functioning. CONCLUSIONS: The levels to which treating teams are perceived as supportive may reflect culturally shaped attitudes (e.g., warmer attitudes towards healthcare providers in India vis-à-vis Canada) and actual differences in how supportive treating teams are, which too may be culturally shaped. Being expected to be more involved in treatment, Chennai families may receive more attention and support, which may further reinforce their involvement. Across contexts, those who improve over follow-up may see their treating teams more positively.
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Familia , Trastornos Psicóticos , Humanos , Femenino , Masculino , India , Adulto , Trastornos Psicóticos/terapia , Adulto Joven , Familia/psicología , Quebec , Canadá , Intervención Médica Temprana , Servicios de Salud Mental/estadística & datos numéricos , Adolescente , Comparación Transcultural , Persona de Mediana EdadRESUMEN
OBJECTIVE: Despite their acknowledged value, patient-reported outcome measures (PROMs) are infrequently used in psychosis, particularly in low-and middle-income countries. We compared ratings on two single-item PROMs, Self-Rated Health (SRH) and Self-Rated Mental Health (SRMH), of persons receiving similar early psychosis services in Chennai, India and Montreal, Canada. We hypothesized greater improvements in SRH and SRMH in the Chennai (compared to the Montreal) sample. METHODS: Participants (Chennai N = 159/168 who participated in the larger study; Montreal N = 74/165 who participated in the larger study) completed the SRH and SRMH during at least two out of three timepoints (entry, months 12 and 24). Repeated measures proportional odds logistic regressions examined the effects of time (baseline to month 24), site, and relevant baseline (e.g., gender) and time-varying covariates (i.e., symptoms) on SRH and SRMH scores. RESULTS: SRH (but not SRMH) scores significantly differed between the sites at baseline, with Chennai patients reporting poorer health (OR: 0.33; CI: 0.18, 0.63). While Chennai patients reported similar significant improvements in their SRH (OR: 7.03; CI: 3.13; 15.78) and SRMH (OR: 2.29, CI: 1.03, 5.11) over time, Montreal patients only reported significant improvements in their SRMH. Women in Chennai (but not Montreal) reported lower mental health than men. Higher anxiety and longer durations of untreated psychosis were associated with poorer SRH and SRMH, while negative symptoms were associated with SRH. CONCLUSIONS: As hypothesized, Chennai patients reported greater improvements in health and mental health. The marked differences between health and mental health in Montreal, in contrast to the overlap between the two in Chennai, aligns with previous findings of clearer distinctions between mind and body in Western societies. Cross-context (e.g., anxiety) and context-specific (e.g., gender) factors influence patients' health perceptions. Our results highlight the value of integrating simple PROMs in early psychosis.
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Comparación Transcultural , Medición de Resultados Informados por el Paciente , Trastornos Psicóticos , Autoinforme , Humanos , Masculino , Femenino , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/terapia , India , Adulto , Estudios Longitudinales , Adulto Joven , Canadá , Adolescente , Salud Mental , Quebec/epidemiologíaRESUMEN
PURPOSE: Breast cancer (BC) is the most frequently diagnosed cancer among women. Approximately 40% of BC survivors are diagnosed during the peak years of their professional career. Women face numerous obstacles when returning to work (RTW) after BC. Their decision-making process and self-efficacy to overcome these barriers may undergo alterations. The objective of this study was to validate the Return-to-work Obstacles and Self-Efficacy Scale (ROSES) for BC survivors, with a focus on three psychometric properties: construct validity, test-retest reliability, and predictive validity. METHODS: This prospective study consists of three phases: Phase 1 (baseline, during sick leave) was conducted to evaluate construct validity, Phase 2 (2 weeks later) assessed test-retest reliability, and Phase 3 (6-month follow-up, RTW or not) aimed to evaluate predictive validity. A total of 153 BC survivors participated in Phase 1 of the study, where they completed the 10 dimensions of the ROSES (e.g., fear of relapse, cognitive difficulties). Confirmatory factor analyses (CFA), Pearson correlations, and Cox regressions were performed, with respect to each phase. RESULTS: The mean duration for RTW with the same employer was 62.7 weeks. CFAs confirmed the ROSES structure, which had previously been established for other health conditions, showing satisfactory coefficients. Significant Pearson correlation coefficients were observed between the ROSES dimensions from Phase 1 to Phase 2, ranging from 0.66 to 0.88. When considering various confounding variables, chemotherapy treatment and cognitive difficulties (ROSES dimension) emerged as the only significant predictors of RTW. CONCLUSION: These findings support the utilization of the ROSES in clinical and research settings for BC survivors to improve their successful RTW. After an initial screening using the ROSES, occupational health professionals can further conduct a focused and thorough evaluation of specific dimensions, such as cognitive difficulties. Additional research and information are required to assist BC survivors in dealing with cognitive impairments induced by chemotherapy when they return to work.
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BACKGROUND: Data from high-income countries (HICs) show a high risk of suicidal thoughts and behaviors (STBs) in first-episode psychosis (FEP). It is unknown, however, whether rates and associated factors differ in low- and middle-income countries (LMICs). AIMS: We therefore aimed to compare the 2-year course of STBs and associated factors in persons with FEP treated in two similarly structured early intervention services in Chennai, India and Montreal, Canada. METHOD: To ensure fit to the data that included persons without STBs and with varying STBs' severity, a hurdle model was conducted by site, including known predictors of STBs. The 2-year evolution of STBs was compared by site with mixed-effects ordered logistic regression. RESULTS: The study included 333 FEP patients (168 in Chennai, 165 in Montreal). A significant decrease in STBs was observed at both sites (OR = 0.87; 95% CI [0.84, 0.90]), with the greatest decline in the first 2 months of follow-up. Although three Chennai women died by suicide in the first 4 months (none in Montreal), Chennai patients had a lower risk of STBs over follow-up (OR = 0.44; 95% CI [0.23, 0.81]). Some factors (depression, history of suicide attempts) were consistently associated with STBs across contexts, while others (gender, history of suicidal ideation, relationship status) were associated at only one of the two sites. CONCLUSIONS: This is the first study to compare STBs in FEP between two distinct geo-sociocultural contexts (an HIC and an LMIC). At both sites, STBs reduced after treatment initiation, suggesting that early intervention reduces STBs across contexts. At both sites, for some patients, STBs persisted or first appeared during follow-up, indicating need for suicide prevention throughout follow-up. Our study demonstrates contextual variations in rates and factors associated with STBs. This has implications for tailoring suicide prevention and makes the case for more research on STBs in FEP in diverse contexts.
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Comparación Transcultural , Trastornos Psicóticos , Ideación Suicida , Humanos , Femenino , Masculino , India , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/psicología , Adulto , Adulto Joven , Prevalencia , Adolescente , Intento de Suicidio/estadística & datos numéricos , Intento de Suicidio/psicología , Factores de Riesgo , Quebec/epidemiología , Modelos Logísticos , Canadá/epidemiologíaRESUMEN
OBJECTIVE: The At Home/Chez Soi trial for homeless individuals with mental illness showed scattered-site Housing First with Assertive Community Treatment (ACT) to be more effective than treatment as usual. This study evaluated the cost-effectiveness of Housing First with ACT and treatment as usual. METHODS: Between October 2009 and June 2011, a total of 950 homeless individuals with serious mental illness were recruited in five Canadian cities: Vancouver, Winnipeg, Toronto, Montreal, and Moncton. Participants were randomly assigned to Housing First (N=469) or treatment as usual (N=481) and followed up for up to 24 months. The intervention consisted of scattered-site Housing First, using rent supplements, with ACT. The treatment-as-usual group had access to all other services. The perspective of society was adopted for the cost-effectiveness analysis. Days of stable housing served as the outcome measure. Retrospective questionnaires captured service use data. RESULTS: Most (69%) of the costs of the intervention were offset by savings in other costs, such as emergency shelters, reducing the net annual cost of the intervention to about Can$6,311 per person. The incremental cost-effectiveness ratio was Can$41.73 per day of stable housing (95% confidence interval=Can$1.96-$83.70). At up to Can$60 per day, Housing First had more than an 80% chance of being cost-effective, compared with treatment as usual. Cost-effectiveness did not vary by participant characteristics. CONCLUSIONS: Housing First with ACT appeared about as cost-effective as Housing First with intensive case management for people with moderate needs. The optimal mix between the two remains to be determined.
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Servicios Comunitarios de Salud Mental , Personas con Mala Vivienda , Trastornos Mentales , Canadá , Análisis Costo-Beneficio , Vivienda , Humanos , Trastornos Mentales/terapia , Estudios RetrospectivosRESUMEN
Importance: In the At Home/Chez Soi trial for homeless individuals with mental illness, the scattered-site Housing First (HF) with Intensive Case Management (ICM) intervention proved more effective than treatment as usual (TAU). Objective: To evaluate the cost-effectiveness of the HF plus ICM intervention compared with TAU. Design, Setting, and Participants: This is an economic evaluation study of data from the At Home/Chez Soi randomized clinical trial. From October 2009 through July 2011, 1198 individuals were randomized to the intervention (n = 689) or TAU (n = 509) and followed up for as long as 24 months. Participants were recruited in the Canadian cities of Vancouver, Winnipeg, Toronto, and Montreal. Participants with a current mental disorder who were homeless and had a moderate level of need were included. Data were analyzed from 2013 through 2019, per protocol. Interventions: Scattered-site HF (using rent supplements) with off-site ICM services was compared with usual housing and support services in each city. Main Outcomes and Measures: The analysis was performed from the perspective of society, with days of stable housing as the outcome. Service use was ascertained using questionnaires. Unit costs were estimated in 2016 Canadian dollars. Results: Of 1198 randomized individuals, 795 (66.4%) were men and 696 (58.1%) were aged 30 to 49 years. Almost all (1160 participants, including 677 in the HF group and 483 in the TAU group) contributed data to the economic analysis. Days of stable housing were higher by 140.34 days (95% CI, 128.14-153.31 days) in the HF group. The intervention cost $14â¯496 per person per year; reductions in costs of other services brought the net cost down by 46% to $7868 (95% CI, $4409-$11â¯405). The incremental cost-effectiveness ratio was $56.08 (95% CI, $29.55-$84.78) per additional day of stable housing. In sensitivity analyses, adjusting for baseline differences using a regression-based method, without altering the discount rate, caused the largest change in the incremental cost-effectiveness ratio with an increase to $60.18 (95% CI, $35.27-$86.95). At $67 per day of stable housing, there was an 80% chance that HF was cost-effective compared with TAU. The cost-effectiveness of HF appeared to be similar for all participants, although possibly less for those with a higher number of previous psychiatric hospitalizations. Conclusions and Relevance: In this study, the cost per additional day of stable housing was similar to that of many interventions for homeless individuals. Based on these results, expanding access to HF with ICM appears to be warranted from an economic standpoint. Trial Registration: isrctn.org Identifier: ISRCTN42520374.
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Manejo de Caso/economía , Análisis Costo-Beneficio , Vivienda/economía , Personas con Mala Vivienda/psicología , Trastornos Mentales/terapia , Adulto , Canadá , Femenino , Estudios de Seguimiento , Humanos , Masculino , Trastornos Mentales/economía , Persona de Mediana EdadRESUMEN
BACKGROUND: Limited evidence on the costs of homelessness in Canada is available. We estimated the average annual costs, in total and by cost category, that homeless people with mental illness engender from the perspective of society. We also identified individual characteristics associated with higher costs. METHODS: As part of the At Home/Chez Soi trial of Housing First for homeless people with mental illness, 990 participants were assigned to the usual-treatment (control) group in 5 Canadian cities (Vancouver, Winnipeg, Toronto, Montréal and Moncton) between October 2009 and June 2011. They were followed for up to 2 years. Questionnaires ascertained service use and income, and city-specific unit costs were estimated. We adjusted costs for site differences in sample characteristics. We used generalized linear models to identify individual-level characteristics associated with higher costs. RESULTS: Usable data were available for 937 participants (94.6%). Average annual costs (excluding medications) per person in Vancouver, Winnipeg, Toronto, Montréal and Moncton were $53â¯144 (95% confidence interval [CI] $46â¯297-$60â¯095), $45â¯565 (95% CI $41â¯039-$50â¯412), $58â¯972 (95% CI $52â¯237-$66â¯085), $56â¯406 (95% CI $50â¯654-$62â¯456) and $29â¯610 (95% CI $24â¯995-$34â¯480), respectively. Net costs ranged from $15â¯530 to $341â¯535. Distributions of costs across categories varied significantly across cities. Lower functioning and a history of psychiatric hospital stays were the most important predictors of higher costs. INTERPRETATION: Homeless people with mental illness generate very high costs for society. Programs are needed to reorient this spending toward more effectively preventing homelessness and toward meeting the health, housing and social service needs of homeless people.
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Individual placement and support (IPS) has not been tested experimentally among people recently housed with a scattered-site Housing First program. Ninety recently housed people were randomized to IPS or usual services. Regression models estimated via GEE were used to compare employment outcomes. Over 8 months of follow-up with good fidelity, fifteen (34 %) people in the IPS group versus nine (22 %) in the control group found competitive employment (p = 0.16). Adjusted odds of obtaining competitive employment were greater in the IPS group (OR 2.42, 95 %CI 1.13-5.16). Other employment outcomes were not significantly different between groups. Satisfaction with services was greater in the group receiving IPS. In this study, IPS was a modestly useful adjunct to scattered-site Housing First for people with mental illness who have been homeless.
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Empleos Subvencionados/psicología , Empleos Subvencionados/estadística & datos numéricos , Personas con Mala Vivienda/psicología , Personas con Mala Vivienda/estadística & datos numéricos , Trastornos Mentales/rehabilitación , Rehabilitación Vocacional/métodos , Adulto , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto JovenRESUMEN
IMPORTANCE: Scattered-site housing with Intensive Case Management (ICM) may be an appropriate and less-costly option for homeless adults with mental illness who do not require the treatment intensity of Assertive Community Treatment. OBJECTIVE: To examine the effect of scattered-site housing with ICM services on housing stability and generic quality of life among homeless adults with mental illness and moderate support needs for mental health services. DESIGN, SETTING, AND PARTICIPANTS: The At Home/Chez Soi project was an unblinded, randomized trial. From October 2009 to July 2011, participants (N = 1198) were recruited in 4 Canadian cities (Vancouver, Winnipeg, Toronto, and Montreal), randomized to the intervention group (n = 689) or usual care group (n = 509), and followed up for 24 months. INTERVENTIONS: The intervention consisted of scattered-site housing (using rent supplements) and off-site ICM services. The usual care group had access to existing housing and support services in their communities. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of days stably housed during the 24-month period following randomization. The secondary outcome was generic quality of life, assessed by a EuroQoL 5 Dimensions (EQ-5D) health questionnaire. RESULTS: During the 24 months after randomization, the adjusted percentage of days stably housed was higher among the intervention group than the usual care group, although adjusted mean differences varied across sites. [table: see text] The mean change in EQ-5D score from baseline to 24 months among the intervention group was not statistically different from the usual care group (60.5 [95%CI, 58.6 to 62.5] at baseline and 67.2 [95%CI, 65.2 to 69.1] at 24 months for the intervention group vs 62.1 [95% CI, 59.9 to 64.4] at baseline and 68.6 [95%CI, 66.3 to 71.0] at 24 months for the usual care group, difference in mean changes, 0.10 [95%CI, −2.92 to 3.13], P=.95). CONCLUSIONS AND RELEVANCE: Among homeless adults with mental illness in 4 Canadian cities, scattered site housing with ICM services compared with usual access to existing housing and community services resulted in increased housing stability over 24 months, but did not improve generic quality of life. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN42520374.
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Manejo de Caso , Personas con Mala Vivienda , Trastornos Mentales/rehabilitación , Vivienda Popular , Adulto , Canadá , Manejo de Caso/economía , Servicios Comunitarios de Salud Mental/economía , Costos y Análisis de Costo , Femenino , Personas con Mala Vivienda/psicología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study investigated the role of psychological variables and judicial problems in treatment retention for a low-threshold methadone program in Montreal, Canada. Logistic regression analyses were computed to examine associations between psychological variables (psychological distress, self-esteem, stages of change), criminal justice involvement, and treatment retention for 106 highly-disorganized opioid users. Higher methadone dosage was associated with increased odds of treatment retention, whereas criminal charges and lower self-esteem decreased these odds. Psychological variables could be identified early in treatment and targeted to increase potential treatment retention. Financial support for this study was provided by the Fonds de Recherche en Santé du Québec.
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Cumplimiento de la Medicación/psicología , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos/psicología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adolescente , Adulto , Crimen/psicología , Crimen/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Trastornos Relacionados con Opioides/psicología , Quebec/epidemiología , Autoimagen , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Adulto JovenRESUMEN
This study assesses the Urban Breakaway Project, a collaborative project offering a structured vacation in the countryside of the province of Quebec intended for homeless (or street) youths. The objective of this study was to document participants' perspectives regarding this project by examining their satisfaction, intention to change following their stay and perceived improvement with respect to their life situation. Another goal of this research was to investigate the relationship between satisfaction level and perceived improvement of participants. One hundred and seven individuals participated in the study, during Urban Breakaway's first year of operation. Satisfaction with the project, assessed with the global Client Satisfaction Questionnaire-3 score, revealed a positive relationship with global scores of perceived improvement, as measured by the Perceived Improvement Questionnaire [PIQ; r = 0.37 (67), 95% CI (0.15; 0.56)]. Regarding intention to change, the data indicated that 95% of participants had moderate-to-definite intentions to do something to change their lives. Participants reported an improvement for most items covered by the PIQ. They experienced the greatest changes in relation to mood, leisure, appetite, physical condition and self-esteem. Results indicate that the Urban Breakaway Project reaches not only street youths but also an older homeless population. Participants, regardless of their age, were found to be very satisfied with services obtained, and their satisfaction was significantly correlated with the perceived improvement in their situation. Qualitative data indicate that characteristics of the programme, such as the countryside setting, the focus on basic needs, the climate and the opportunity for socialisation, peer support (or belonging) and personal growth were appreciated.
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Redes Comunitarias , Comportamiento del Consumidor , Personas con Mala Vivienda/psicología , Actividades Recreativas , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Quebec , Encuestas y Cuestionarios , Adulto JovenRESUMEN
How should case management be organized for people who have severe mental illness, but do not need Assertive Community Treatment or similar high-intensity programs? To address this question, the authors conducted a systematic review of studies published in English between 1980 and 2010. Five main case management models were identified: broker, clinical case management, rehabilitation, strengths and intensive case management. In all, 11 experimental and 13 quasi-experimental studies evaluating case management programs not targeted at a typical ACT clientele were identified. These studies suggest that the strengths model, which can be viewed as a way of structuring intensive case management for a moderate-need population, is the best supported by evidence if one desires to see effects not only on hospital days, but also on other domains such as symptoms, quality of life and social functioning. It is also compatible with a recovery orientation. The evidence in its favor, however, remains modest.
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Manejo de Caso , Servicios de Salud Mental/organización & administración , Humanos , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: The objective of this study was to evaluate the relationship between perceived improvement and client satisfaction in a methadone maintenance treatment population. A secondary objective was to evaluate the psychometric properties of the Perceived Improvement Questionnaire (PIQ). DATA SOURCES/STUDY SETTING: Two hundred and thirty-two clients of a methadone maintenance treatment program filled out self-reported questionnaires and two open-ended questions measuring their perceived improvement and their level of satisfaction with the services received. PRINCIPAL FINDINGS: Correlation analyses revealed a significant relationship between participants' perceived improvement and their level of satisfaction with services received throughout their treatment. A factor analysis identified 3 sub-scales of the PIQ: emotional health, social relations and physical health. The PIQ's internal consistency and construct validity supported the adequacy of the metric properties of the questionnaire. CONCLUSION: Further research is needed to investigate the link between clients' input and treatment satisfaction in different substance abuse populations. The scale's potential to provide valuable information such as clinical assessment and program evaluation should be explored.
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Metadona/uso terapéutico , Satisfacción del Paciente , Evaluación de Programas y Proyectos de Salud/métodos , Adulto , Atención Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVE: To document compliance with medical and psychosocial appointments for HIV/AIDS treatment in a population of marginalized individuals with problematic drug use. METHOD: This is a retrospective study exploring appointment compliance for an HIV treatment based on an outreach intervention. Information regarding the medical and psychosocial appointments of 185 patients of the HIV-Drug Addiction outpatient unit, at the University of Montreal Hospital Centre (CHUM), has been collected for a one-year period (2006-2007). The compliance rate of appointments has been calculated according to the type of care provided: 1) conventional, provided only in the clinic at the "fixed" location, and 2) outreach-based, when the team at the fixed location is complemented by the intervention of a "mobile" team for the more unstable patients. RESULTS: Compliance rates for medical and psychosocial appointments in patients receiving care solely at the fixed location is 61.4%. For those whom care is received at the fixed location while complemented by the mobile team, the corresponding rate is 73.9%. This is an elevated compliance rate, higher than those generally reported for outreach-based programs. CONCLUSION: These results lend support to the success of programs integrating an outreach-based intervention for a vulnerable clientele. Indeed, appointment compliance in those who are more disorganized, for which the mobile team has intervened, has proven comparable and even superior to compliance with appointments when treatment is only received at the fixed location.
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Citas y Horarios , Documentación , Infecciones por VIH/tratamiento farmacológico , Cooperación del Paciente , Trastornos Relacionados con Sustancias , Poblaciones Vulnerables , Adulto , Femenino , Infecciones por VIH/psicología , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Quebec , Estudios RetrospectivosRESUMEN
A rapid and efficient synthesis of a series of C2-symmetric 17beta-estradiol homo-dimers is described. The new molecules are linked at position 17alpha of the steroid nucleus with either an alkyl chain or a polyethylene glycol chain. They are made from estrone in only five chemical steps with an overall yield exceeding 30%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER+ and ER-) human breast tumor cell lines: MCF-7 and MDA-MB-231. Some of the dimers present selective cytotoxic activity against the ER+ cell line. However, they are not very cytotoxic when compared to the antiestrogen tamoxifen. Unfortunately, they show only weak affinity for the estrogen receptor alpha (ERalpha) and no affinity for the estrogen receptor beta (ERbeta). The new compounds were also tested on human intestinal (HT-29) cancer and on murine skin cancer (B16-F10) cell lines for further biological assessment. Interestingly, the dimers were found to be cytotoxic to the murine skin cancer cell line but were inactive towards the intestinal cancer cell line.
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Estradiol/síntesis química , Estradiol/farmacología , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Neoplasias de la Mama , Línea Celular Tumoral , Dimerización , Estradiol/química , Humanos , Neoplasias Intestinales , Espectroscopía de Resonancia Magnética , Unión Proteica , Neoplasias Cutáneas , Espectrofotometría InfrarrojaRESUMEN
The synthesis of two new highly potent 17beta-estradiol-linked platinum(II) complexes is described. The new molecules are linked at position 16 of the steroid nucleus with an alkyl chain. They are made from estrone in nine chemical steps with an overall yield exceeding 10%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human breast tumor cell lines: MCF-7 and MDA-MB-231. The novel compounds prove to be highly cytotoxic against breast cancer cell lines. The most cytotoxic derivative shows high affinity for the estrogen receptor alpha.
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Antineoplásicos/síntesis química , Neoplasias de la Mama/patología , Estradiol/análogos & derivados , Estradiol/síntesis química , Compuestos Organoplatinos/síntesis química , Antineoplásicos/farmacología , Estradiol/farmacología , Receptor alfa de Estrógeno/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Concentración 50 Inhibidora , Compuestos Organoplatinos/farmacología , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
A rapid and efficient synthesis of a series of C(2)-symmetric 17 beta-estradiol dimers is described. The new molecules are linked at position 17 alpha of the steroid nucleus with either an alkyl chain or a polyethylene glycol chain. They are made from estrone in five chemical steps with an overall yield exceeding 30%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human breast tumor cell lines: MCF-7 and MDA-MB-231. Some of the dimers present selective cytotoxic activity against the ER(+) cell line.