RESUMO
The consequences of the systemic errors in policies, research, and education that exclude women are still being faced. Consequently, women have higher morbidity and mortality rates in many conditions with high public health significance. Here we discuss important gaps in policy, research, and education that result in worse health outcomes for women.
Assuntos
Políticas , Saúde Pública , Escolaridade , Feminino , Serviços de Saúde , Humanos , MorbidadeRESUMO
Women were historically excluded from clinical trials. Despite numerous guidance and policy, we are still seeing this exclusion throughout the research pipeline more than 40 years later. The progress that has been made to include women in clinical trials and to report data disaggregated by sex continues to be limited due to multiple factors. In this paper, we aim to review some of the current FDA funding, policies, and practice in regard to inclusion of biological sex and sociocultural gender variables. This paper provides some recommendations and actionable policies to ensure that women as well as men can benefit from the updated biomedical research and clinical trials designed to take these variables into account. Strong regulations and mandates should be in place to direct pharmaceutical companies and industry toward the inclusion of women in biomedical research instead of a series of guidelines and recommendations that have not led to sufficient progress. Additionally, regulatory agencies should be completely independent in their decision-making process. Provision of Food and Drug Administration (FDA) funding by industry user fee for instance, might compromise FDA's impartiality in the approval process. Finally, better oversight is needed by the FDA for the labeling of drugs. FDA has made a significant contribution to the progress that has been made to this date, however, some of the current action plans including the Drug Trial Snapshots need to be refined to be more responsive to the current needs.
Assuntos
Ensaios Clínicos como Assunto , United States Food and Drug Administration , Aprovação de Drogas , Feminino , Humanos , Masculino , Estados UnidosRESUMO
A 2001 U.S. Government Accountability Office (GAO) report indicated 8 of 10 drugs withdrawn from the U.S. market between 1997 and 2000 posed greater risk to women than men. We examined drugs withdrawn from the market for safety-related reasons from January 1, 2001, to January 1, 2018. To be included, drugs must be listed as discontinued on Drugs@FDA and either listed in the Federal Register or cited in literature as being withdrawn for safety-related reasons. Biologics, over-the-counter products, and medical devices were excluded. During the 17-year time span, 19 drugs were withdrawn from the market for safety-related reasons, fewer drugs per year compared to the 3-year period examined in the GAO report. Food and Drug Administration (FDA) has not recommended the market removal of any drug approved since 2005 due to the time from the start of the Q wave to the end of the T wave (QT) interval prolongation resulting in torsades de pointes (TdP) or other abnormal heart rhythms. Furthermore, no drugs approved after the implementation of FDA's 2009 guidance on drug-induced liver injury (DILI) have been withdrawn because of hepatoxicity. All, but one of the drugs discontinued from the market for safety-related reasons during the period examined were approved between 1957 and 2002. TdP and DILI are two relevant examples of drug-induced adverse events posing greater risk to women than men. FDA has made measurable progress incorporating consideration of sex and gender differences into drug trial development and FDA review of these data, supporting inclusion of women in clinical trials, providing a comprehensive drug safety review, and advancing postmarket surveillance and risk assessment, thus strengthening FDA's ability to protect public health.
Assuntos
Preparações Farmacêuticas , Feminino , Humanos , Masculino , Medicamentos sem Prescrição , Responsabilidade Social , Estados Unidos , United States Food and Drug AdministrationRESUMO
Background: Graduates of simulation fellowship programmes are expected to have the ability to perform a variety of simulation specific skills at the time of graduation. Currently, simulation fellowship directors have access to tools to assess the ability of a fellow to debrief learners. However, there is no tool to assess a simulation fellow's competency in technical skills. The purpose of our manuscript was to develop and obtain content validation of a novel instrument designed to assess a simulation fellow's ability to perform the five core simulation technical skills. Methods: The study protocol was based on a methodology for content validation of curriculum consensus guidelines. This approach involves a three-step process, which includes the initial delineation of the curricular content. This was then followed by the validation of the curricular content using survey methodology and lastly obtaining consensus on modifications using Delphi methodology. Results: Two rounds of modified Delphi methodology were performed. Seventy-four respondents provided feedback on the round 1 survey and 45 respondents provided feedback on round 2. The final assessment tool has five elements and 16 subitems with four optional subitems. Conclusion: The Evaluation of Technical Competency in Healthcare Simulation tool provides an instrument developed from a national consensus of content experts. This tool provides simulation fellowship directors a method to evaluate fellows' competency in technical skills.
RESUMO
CONTEXT: Generic drugs account for 9 out of 10 prescriptions dispensed in the United States but for a lower proportion of commonly prescribed thyroid hormone replacement therapies. OBJECTIVE: Characterize temporal patterns of generic and brand-name thyroid hormone drug use, including patient and prescriber characteristics associated with brand-name use. DESIGN AND SETTING: Cross-sectional longitudinal analysis of national data from a large administrative claims database from January 2007 through December 2016. PATIENTS: Adults with insurance coverage through commercial, Medicare Advantage, and Medicare Part D health plans. MAIN OUTCOME MEASURES: Generic and brand-name thyroid hormone drug use. RESULTS: From 2007 to 2016, the annual number of thyroid hormone treatment pharmacy fills increased from 8,905,836 in 2007 to 11,613,923 in 2016, 73.6% of which were for generic levothyroxine, 23.4% for brand-name levothyroxine, and the remaining for other formulations. Dispensing of generic thyroid hormone drugs increased from 59.8% in 2007 to 84.9% in 2016 and was consistently higher among Medicare Advantage and Medicare Part D when compared with the commercial beneficiary population. For all three beneficiary populations, use of brand-name products was less common among older adults and more common among women and those receiving prescriptions from endocrinologists and was more common among those of white race and with greater household income for the Medicare Advantage and commercial beneficiary populations (P < 0.001). CONCLUSIONS: Brand-name thyroid hormone product use declined from 2007 to 2016 among three large, national insurer beneficiary populations. Although certain patient characteristics were associated with brand-name use, prescriber specialty was the strongest predictor.
Assuntos
Medicamentos Genéricos/uso terapêutico , Medicare Part D , Hormônios Tireóideos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Estados UnidosRESUMO
Historically, women have been underrepresented in clinical research, requiring physicians to extrapolate medical recommendations for women from clinical research done in cohorts consisting predominantly of male participants. While government-funded clinical research has achieved gender parity in phase-3 clinical trials across many biomedical disciplines, improvements are still needed in several facets of women's health research, such as the inclusion of women in early-phase clinical trials, the inclusion of pregnant women and women with physical and intellectual disabilities, the consideration of sex as a biological variable in preclinical research, and the analysis and reporting of sex and gender differences across the full biomedical research continuum. The National Institutes of Health (NIH) Office of Research on Women's Health and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the 25th Annual Women's Health Congress, held in Arlington, VA in April, 2017, to highlight gains made and remaining needs regarding the representation of women in clinical research, to introduce innovative procedures and technologies, and to outline revised policy for future studies. Six speakers presented information on a range of subjects related to the representation of women in clinical research and federal initiatives to advance precision medicine. Topics included the following: the return on investment from the NIH-funded Women's Health Initiative; progress in including women in clinical trials for FDA-approved drugs and products; the importance of clinical trials in pregnant women; FDA initiatives to report drug safety during pregnancy; the NIH-funded All of Us Research Program; and efforts to enhance FDA transparency and communications, including the introduction of Drug Trials Snapshots. This article summarizes the major points of the presentations and the discussions that followed.
Assuntos
Pesquisa Biomédica , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos/organização & administração , Seleção de Pacientes , Sexismo/prevenção & controle , Saúde da Mulher , Pesquisa Biomédica/economia , Pesquisa Biomédica/ética , Pesquisa Biomédica/normas , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/normas , Feminino , Administração Financeira/métodos , Humanos , Avaliação das Necessidades , Gestantes , Melhoria de Qualidade , Estados UnidosRESUMO
BACKGROUND: Concerns exist that women are underrepresented in trials of cardiovascular medications. OBJECTIVES: The authors sought to examine women's participation and the reported safety and efficacy by gender for pivotal cardiovascular disease (CVD) trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. METHODS: On the basis of publicly available FDA reviews, the authors assessed enrollment of women in trials supporting 36 drug approvals from 2005 to 2015. Prevalence-corrected estimates for the participation of women were calculated as the percentage of women among trial participants divided by the percentage of women in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of women in the trial and disease population. Sex differences in efficacy and safety were assessed. RESULTS: The proportion of women enrolled ranged from 22% to 81% (mean 46%). The calculated PPR by disease area was within or above the desirable range for atrial fibrillation (0.8 to 1.1), hypertension (0.9), and pulmonary arterial hypertension (1.4); PPR was <0.8 for heart failure (0.5 to 0.6), coronary artery disease (0.6), and acute coronary syndrome/myocardial infarction (0.6). The authors found little indication of clinically meaningful gender differences in efficacy or safety. Gender differences in efficacy or safety were described in labeling for 4 drugs. CONCLUSIONS: Women were well represented in trials of drugs for hypertension and atrial fibrillation, and overrepresented for pulmonary arterial hypertension. Representation of women fell below a PPR of 0.8 for trials in heart failure, coronary artery disease, and acute coronary syndrome. Minimal gender differences in drug efficacy and safety profiles were observed.
Assuntos
Fármacos Cardiovasculares , Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas , Feminino , Humanos , Masculino , Fatores Sexuais , MulheresRESUMO
PURPOSE: The goal of this study was to determine the association between cardiorespiratory fitness (CRF) and bone mineral density (BMD) of the femoral neck (FN) in postmenopausal women using existing Cooper Center Longitudinal Study data. MATERIALS AND METHODS: A cohort of 1,720 predominantly healthy Caucasian women (57.1 ± 6.9 years) underwent preventive medical examinations that included CRF assessment by maximal Balke treadmill testing and measurement of BMD by dual-energy X-ray absorptiometry. CRF was estimated from total treadmill time and categorized into five categories of CRF (further defined as fitness category 1 = low fitness, 2-3 = moderate fitness, and 4-5 = high fitness). Logistic regression was used to characterize the association between CRF and BMD, adjusting for age, weight, and resistance activity level. RESULTS: Overall, the mean body-mass index (BMI) for all subjects was 25.0 ± 4.5 kg/m2, although BMI was in the obese range in the low fitness group. The prevalence of osteoporosis (T-score ≤ -2.5 at the FN) was greater in the low fit group than moderate or high fit (5.8% vs. 3.0% or 3.9%, respectively); with a similar pattern seen for prevalence of osteopenia (T-score > -2.5 and ≤ -1.0 at the FN) (47.5% vs. 46.4% or 44.8%, respectively). Higher age and lower weight were associated with low BMD. Fully adjusted logistic regression models showed an inverse association between CRF and low BMD of the FN. For T-score ≤ -1.0, the primary outcome, the odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.32-0.79) for moderate fitness, and OR of 0.32 (95% CI 0.21-0.51) for high fitness was seen. For T-score ≤ -2.5 at the FN, OR was 0.30 (95% CI 0.11-0.80) for moderate fitness, and OR was 0.29 (95% CI 0.12-0.71) for high fitness. CONCLUSION: Increased CRF levels are associated with reduced risk for low bone density in postmenopausal women.
Assuntos
Densidade Óssea/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Colo do Fêmur/patologia , Osteoporose/epidemiologia , Pós-Menopausa , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Aptidão Física , Prevalência , Estudos Retrospectivos , Fatores de Risco , Texas/epidemiologiaRESUMO
BACKGROUND: Gender- and sex-specific medicine is defined as the practice of medicine based on the understanding that biology (dictated by sex chromosomes) and social roles (gender) are important in and have implications for prevention, screening, diagnosis, and treatment in men and women. In light of the many ways that sex and gender influence disease presentation and patient management, there have been various initiatives to improve the integration of these topics into medical education curriculum. Although certain schools may include the topics, their impact on the student body's knowledge has not been as fully studied. By studying the opinions of US allopathic and osteopathic-enrolled students on the extent to which their schools address these topics and their understanding of these topics, this study examined the role of gender specific medicine in the US medical school curriculum. METHODS: An email solicitation with link to an anonymous survey was sent to approximately 35,876 student members of five US medical student organizations. The survey instrument consisted of yes/no, multiple choice, and attitude awareness questions. Data was analyzed as a complete data set to evaluate national trends and via subset analysis using chi-square, paired t test, and one-way anova. RESULTS: A total of 1097 students responded. The majority of respondents strongly agreed that sex and gender medicine (SGBM) improves patient management (96.0 %) and should be included as a part of the medical school curriculum (94.4 %). Only 2.4 % of participants agreed that SGBM is the same as Women's Health. When asked specifically about inclusion of an identified sex and gender-based medicine curriculum at their institution, students answered not sure at 40.8, 25.1, 19.1, and 20.3 % from first year to fourth year, respectively. Males reported a higher rate of exposure to SGBM content areas (in medical history taking, domestic violence) than women. CONCLUSIONS: Medical students recognize the differentiation between SGBM principles and women's health, and understand the translational value of sex and gender-specific principles in the clinical setting. However, current curricular offerings fall short of providing students with adequate coverage of specific evidence-based health differences.
RESUMO
Sex- and Gender-Based Medicine (SGBM) is an emerging discipline within healthcare research, education, and practice. It addresses both the similarities and differences in men and women and it considers both biological and sociocultural factors that impact on the health of all individuals. On a basic level, sex refers to biology and gender refers to sociocultural factors. SGBM emerged after a body of knowledge had been established about health differences between women and men. However, these differences are not consistently considered and misperceptions are propagated when translations from the bench to the bedside are based on a predominantly one-sex model. Medical curricula are not yet integrating the evidence of sex and gender across students' educational experiences. We propose adopting a sex and gender lens to enable physicians and students to critically examine the scientific evidence and assess its applicability to specific patients. A Sex and Gender Medical Education Summit was held in 2015 to create a roadmap for integrating SGBM into medical education. We present examples that led to successful integration of SGBM in U.S. medical schools, as well as resources for medical educators and researchers, so that the health of both women and men can be positively impacted.
Assuntos
Currículo , Educação Médica , Saúde do Homem , Saúde da Mulher , Atenção à Saúde , Feminino , Necessidades e Demandas de Serviços de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Fatores SexuaisRESUMO
BACKGROUND: An effective literature search strategy is critical to achieving the aims of Sex and Gender Specific Health (SGSH): to understand sex and gender differences through research and to effectively incorporate the new knowledge into the clinical decision making process to benefit both male and female patients. The goal of this project was to develop and validate an SGSH literature search tool that is readily and freely available to clinical researchers and practitioners. METHODS: PubMed, a freely available search engine for the Medline database, was selected as the platform to build the SGSH literature search tool. Combinations of Medical Subject Heading terms, text words, and title words were evaluated for optimal specificity and sensitivity. The search tool was then validated against reference bases compiled for two disease states, diabetes and stroke. RESULTS: Key sex and gender terms and limits were bundled to create a search tool to facilitate PubMed SGSH literature searches. During validation, the search tool retrieved 50 of 94 (53.2%) stroke and 62 of 95 (65.3%) diabetes reference articles selected for validation. A general keyword search of stroke or diabetes combined with sex difference retrieved 33 of 94 (35.1%) stroke and 22 of 95 (23.2%) diabetes reference base articles, with lower sensitivity and specificity for SGSH content. CONCLUSIONS: The Texas Tech University Health Sciences Center SGSH PubMed Search Tool provides higher sensitivity and specificity to sex and gender specific health literature. The tool will facilitate research, clinical decision-making, and guideline development relevant to SGSH.
Assuntos
Bases de Dados Bibliográficas , Armazenamento e Recuperação da Informação/métodos , Medical Subject Headings , PubMed , Ferramenta de Busca , Terminologia como Assunto , Feminino , Identidade de Gênero , Humanos , Armazenamento e Recuperação da Informação/normas , MEDLINE , Masculino , Processamento de Linguagem Natural , Reprodutibilidade dos Testes , Fatores SexuaisRESUMO
The field of women's health is varied and dynamic. Major studies in 2014 and the first half of 2015 suggest that selective serotonin reuptake inhibitors are not strongly associated with congenital heart defects, that paroxetine 7.5 mg is effective for treating menopausal symptoms, and that women with heart failure may benefit more from cardiac resynchronization therapy than men.
Assuntos
Competência Clínica , Depressão/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Paroxetina/farmacologia , Saúde da Mulher , Feminino , Humanos , Fatores de Risco , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
PURPOSE OF THE STUDY: Male-based studies, both at the biochemical and at the pre-clinical/clinical trial levels, still predominate in the scientific community. Many studies are based on the wrong assumption that both sexes are fundamentally identical in their response to treatments. As a result, findings obtained mainly in males are applied to females, resulting in negative consequences female patients. In cancer immunotherapy, there is still a scarce focus on this topic. Here we review the main differences in immune modulation and immune system biology between males and females with a particular focus on how these differences affect cancer immunotherapy and cancer vaccines. METHODS: We reviewed articles published on PubMed from 1999 to 2014, using the keywords: sex hormones, immune response, estrogen, immunotherapy, testosterone, cancer vaccines, sex-based medicine. We also present new data wherein the expression of the cancer testis antigen, Ropporin-1, was determined in patients with multiple myeloma, showing that the expression of Ropporin-1 was influenced by sex. RESULTS: Male and female immune systems display radical differences mainly due to the immune regulatory effects of sex hormones. These differences might have a dramatic impact on the immunological treatment of cancer. Moreover, the expression of tumor antigens that can be targeted by anti-cancer vaccines is associated with sex. CONCLUSION: Future clinical trials focusing on cancer immunotherapy will need to take into account the differences in the immune response and in the frequency of target antigen expression between male and females, in order to optimize these anti-cancer immunotherapies of the third millennium.
Assuntos
Vacinas Anticâncer , Hormônios Esteroides Gonadais/imunologia , Imunidade , Imunoterapia , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Ensaios Clínicos como Assunto , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Sexo , Fatores Sexuais , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer.
Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias/terapia , Células-Tronco Neoplásicas/imunologia , Receptores Notch/metabolismo , Animais , Carcinogênese , Autorrenovação Celular , Resistencia a Medicamentos Antineoplásicos , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/imunologia , Transdução de SinaisRESUMO
Cancer immunotherapy comprises different therapeutic strategies that exploit the use of distinct components of the immune system, with the common goal of specifically targeting and eradicating neoplastic cells. These varied approaches include the use of specific monoclonal antibodies, checkpoint inhibitors, cytokines, therapeutic cancer vaccines and cellular anticancer strategies such as activated dendritic cell (DC) vaccines, tumor-infiltrating lymphocytes (TILs) and, more recently, genetically engineered T cells. Each one of these approaches has demonstrated promise, but their generalized success has been hindered by the paucity of specific tumor targets resulting in suboptimal tumor responses and unpredictable toxicities. This review will concentrate on recent advances on the use of engineered T cells for adoptive cellular immunotherapy (ACI) in cancer.
Assuntos
Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/fisiologia , Animais , Engenharia Genética , Humanos , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/genética , Proteínas Recombinantes de Fusão/genética , Linfócitos T/transplanteRESUMO
Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the CTAs, Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in cancer samples, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes from patients' peripheral blood mononuclear cells. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients.
Assuntos
Proteínas de Ancoragem à Quinase A/imunologia , Antígenos de Neoplasias/imunologia , Antígenos de Superfície/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Proteínas de Transporte/imunologia , Imunoterapia , Neoplasias Pulmonares/imunologia , Securina/imunologia , Proteínas de Ancoragem à Quinase A/genética , Proteínas de Ancoragem à Quinase A/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Autoanticorpos/sangue , Proteínas de Ligação a Calmodulina , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Técnicas de Cocultura , Citotoxicidade Imunológica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Securina/genética , Securina/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: Ovarian cancer is the most deadly gynecologic malignancy worldwide. Since the pathogenesis of ovarian cancer is incompletely understood, and there are no available screening techniques for early detection, most patients are diagnosed with advanced, incurable disease. In an effort to develop innovative and effective therapies for ovarian cancer, we tested the effectiveness of Galecti-3C in vitro. This is a truncated, dominant negative form of Galectin-3, which is thought to act by blocking endogenous Galectin-3. METHODS: We produced a truncated, dominant-negative form of Galectin-3, namely Galetic-3C. Ovarian cancer cell lines and primary cells from ovarian cancer patients were treated with Galectin-3C, and growth, drug sensitivity, and angiogenesis were tested. RESULT: We show, for the first time, that Galectin-3C significantly reduces the growth, motility, invasion, and angiogenic potential of cultured OC cell lines and primary cells established from OC patients. CONCLUSIONS: Our findings indicate that Galectin-3C is a promising new compound for the treatment of ovarian cancer.
Assuntos
Galectina 3/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Invasividade Neoplásica , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologiaRESUMO
Here we review the role of Galectins in the molecular pathogenesis of multiple myeloma and ovarian cancer, with a special focus on Glectin-3. Multiple myeloma is the second most common hematologic malignancy worldwide. Because the pathogenesis of multiple myeloma is still incompletely understood, there is no ultimately effective cure, and this cancer results fatal. Ovarian cancer is the most lethal gynecologic malignancy worldwide. Due to the lack of screening techniques for early detection, patients are mostly diagnosed with advanced disease, which results ultimately fatal. Multiple myeloma and ovarian cancer have different biologies, but they share a strong dependence on adhesion with extracellular matrix and other cells. Galectin-3 plays a key role in regulating such adhesive abilities of tumor cells. Here we discuss the outcomes and possible mechanism of action of a truncated, dominant negative form of Galectin-3, Galectin-3C, in these malignancies. Overall, we report that Galectin-3C is a promising new compound for effective adjuvant therapies in advanced, refractory multiple myeloma and ovarian cancer.