RESUMO
Since government-provided annual cervical cytology testing for all Taiwanese women aged 30 years or older became available in 1995, both cervical cancer incidence and death have decreased significantly. However, with the 2018 introduction of the national immunization program for human papillomavirus (HPV) vaccination in all schoolgirls aged 13-15 years old, the positive predictive value of cytology testing is expected to decrease with rising vaccination rates, and therefore a transition to more sensitive HPV-based testing may be needed. This position paper, derived from discussions by a panel of experts in cervical cancer screening, provides short-, medium-, and long-term policy recommendations to manage the transition between cervical screening methods for Taiwan. The recommendations include concrete suggestions regarding testing procedures, standards, accreditation, monitoring, promotion, and implementation. It is hoped that comprehensive preparation and management of this transition will enable Taiwan to repeat the previous successes of the cervical cytology testing program.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Adolescente , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Taiwan , Esfregaço Vaginal , Programas de Rastreamento , PolíticasRESUMO
OBJECTIVE: This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions. METHODS: This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart. RESULTS: Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s). CONCLUSIONS: The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time. KEY POINTS: ⢠Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. ⢠Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.
Assuntos
Doenças dos Anexos , Neoplasias Ovarianas , Humanos , Feminino , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/patologia , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Ultrassonografia , Anexos Uterinos/patologia , Sensibilidade e EspecificidadeRESUMO
STUDY OBJECTIVE: To compare the safety, efficacy, and adverse events of the new mini-adjustable sling system "I-stop-mini" with transobturator midurethral slings "Obtryx" (Boston Scientific, Marlborough, MA) in women with stress urinary incontinence. DESIGN: A single-center, retrospective cohort study. SETTING: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan. PATIENTS: A total of 347 patients who underwent I-stop-mini or Obtryx for stress urinary incontinence treatment. INTERVENTIONS: Midurethral sling with either I-stop-mini or Obtryx. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were objective success and subjective cure rates between the 2 groups. Objective success was evaluated using a 1-hour pad test, and subjective cure was evaluated using a questionnaire score (Incontinence Impact Questionnaire, Urinary Distress Inventory, and International Consultation on Incontinence Questionnaire Short Form). Secondary outcomes were the evaluation of surgical outcomes, operative data, and adverse events between the 2 groups. In total, 171 of 200 I-stop-mini subjects and 127 of 147 Obtryx subjects completed 12 months of follow-up. Regarding the objective success between the I-stop-mini group and the Obtryx group, 1-month postoperative (3.6 ± 5.2 vs 3.9 ± 12.6; p = .765), 6-month postoperative (3.9 ± 5.1 vs 4.2 ± 12.6; p = .848), and 12-month postoperative (4.6 ± 5.6 vs 4.5 ± 13.6; p = .980) 1-hour pad tests showed no significant difference. The 12-month subjective cure rates decreased from 94.7% (1-month postoperative) to 91.2% (12-month postoperative) in the I-stop-mini group and 95.2% (1-month postoperative) to 85.0% (12-month postoperative) in the Obtryx group. Similar and durable efficacy was observed between the 2 groups. The I-stop-mini group had shorter operative times and hospital stays than the Obtryx group; however, both groups showed similar adverse event rates. CONCLUSION: The objective success and subjective cure rates of I-stop-mini did not differ to those of Obtryx. However, long-term data and further prospective studies on I-stop-mini are necessary to arrive at a definite conclusion.
Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Feminino , Seguimentos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Slings Suburetrais/efeitos adversos , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgiaRESUMO
OBJECTIVE: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. DATA SOURCES: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence. TABULATION, INTEGRATION, AND RESULTS: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls. CONCLUSION: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.
Assuntos
Endometriose , Anticoncepcionais Orais Combinados/uso terapêutico , Endometriose/tratamento farmacológico , Endometriose/prevenção & controle , Endometriose/cirurgia , Feminino , Humanos , Metanálise em Rede , Ovariectomia , Período Pós-OperatórioRESUMO
Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Fosfoglicerato Mutase/antagonistas & inibidores , Regulação Alostérica , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos Nus , Camundongos SCID , Estrutura Molecular , Terapia de Alvo Molecular , Transplante de Neoplasias , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacosRESUMO
Phytochemical investigation on the 80% EtOH extract of the whole plants of Zephyranthes grandiflora afforded three new 4a-epi-plicamine-type alkaloids, zephyranthines A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against six glioma cell lines (CHG-5, SH-SY5Y, SHG-44, U251, U343, and GL15). Alkaloids 2 and 3 exhibited significant cytotoxic activities against all tested cell lines with IC50 values of less than 20 µM.
Assuntos
Alcaloides , Amaryllidaceae , Alcaloides/farmacologia , Linhagem Celular Tumoral , Compostos Heterocíclicos de 4 ou mais Anéis , Estrutura MolecularRESUMO
Background: Luteal-phase ovarian stimulation (LPOS) is an alternative in vitro fertilization (IVF) protocol. However, limited data showed the genes expression of cumulus cells (CCs) in LPOS. Therefore, this study aimed to investigate CC genes expression between LPOS and follicular-phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing IVF cycles. Methods: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: NCT03238833). A total of 36 PORs who met the Bologna criteria and underwent IVF cycles were enrolled. Fifteen PORs were allocated to the LPOS group, and 21 PORs were allocated to the FPOS group. The levels of CC genes involved in inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR and compared between the two groups. Results: The number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos and top-quality day-3 embryos, clinical pregnancy rates and live birth rates were similar between the two groups except for significantly high progesterone levels in the LPOS group. The mRNA expression levels of CXCL1 (0.51 vs 1.00, p < 0.001) and PTGES (0.30 vs 1.00, p < 0.01) were significantly lower in the LPOS group than in the FPOS group. The LPOS group had significantly lower mRNA expression of NDUFB7 (0.12 vs 1.00, p < 0.001) and NDUFA4L2 (0.33 vs 1.00, p < 0.01) than the FPOS group. DAPK3 (3.81 vs 1.00, p < 0.05) and BCL6B (2.59 vs 1.00, p < 0.01) mRNA expression was significantly higher in the LPOS group than in the FPOS group. Increased expression of PCK1 (3.13 vs. 1.00, p < 0.001) and decreased expression of LDHC (0.12 vs. 1.00, p < 0.001) were observed in the LPOS group compared to the FPOS group. Conclusions: Our data revealed different CC genes expression involving in inflammation, oxidative phosphorylation, apoptosis and metabolism between LPOS and FPOS in PORs. However, the results are non-conclusive; further large-scale randomized controlled trials are needed to validate the results.
Assuntos
Células do Cúmulo/metabolismo , Fertilização in vitro/métodos , Fase Luteal/fisiologia , Indução da Ovulação/métodos , Adulto , Células do Cúmulo/efeitos dos fármacos , Feminino , Fertilização in vitro/estatística & dados numéricos , Hormônio Foliculoestimulante/administração & dosagem , Fase Folicular/efeitos dos fármacos , Fase Folicular/fisiologia , Perfilação da Expressão Gênica , Humanos , Infertilidade/terapia , Nascido Vivo , Fase Luteal/efeitos dos fármacos , Hormônio Luteinizante/administração & dosagem , Recuperação de Oócitos/estatística & dados numéricos , Indução da Ovulação/estatística & dados numéricos , Projetos Piloto , Gravidez , Taxa de Gravidez , Estudos Prospectivos , RNA Mensageiro/metabolismo , Proteínas Recombinantes/administração & dosagem , Resultado do TratamentoRESUMO
Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman's syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate-carboxymethylcellulose or polyethylene oxide-sodium carboxymethylcellulose as anti-adhesive barrier.
Assuntos
Endométrio/patologia , Doenças Uterinas/prevenção & controle , Útero/patologia , Feminino , Humanos , Gravidez , Prevenção Primária , Aderências Teciduais , Doenças Uterinas/etiologia , Doenças Uterinas/patologiaRESUMO
Polycystic ovary syndrome (PCOS), which affects 5-10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine-cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.
Assuntos
Cisteína/metabolismo , Letrozol/farmacologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Receptores CCR5/metabolismo , Receptores de Quimiocinas/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diestro/efeitos dos fármacos , Diestro/metabolismo , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Glucose/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Ovário/metabolismo , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Testosterona/metabolismoRESUMO
Recurrent implantation failure (RIF) remains a clinical dilemma. Helium-Neon (He-Ne) laser irradiation has recently become more popular under certain clinical conditions. Given the unique therapeutic effects, we were interested in determining whether pretreatment with He-Ne laser irradiation prior to frozen-thawed embryo transfer (FET) would improve the microcirculation and cause the release of growth factors and cytokines, thus improving endometrial receptivity and the clinical pregnancy rates. Patients chose for themselves whether to proceed with (n = 29) or without (n = 31) pretreatment with He-Ne laser irradiation prior to FET. The clinical pregnancy rate (37.9%) and implantation rate (20.3%) were higher in the laser-treatment group than in the control group (35.5% and 15.9%, respectively, p = .844 and .518, respectively). The live birth rate was higher in the laser-treatment group (27.6% vs. 25.8%, respectively, p = .876) and the miscarriage rate was lower in the laser-treatment group (18.2% and 27.3%, respectively, p = .611). No side effects or complications from laser irradiation were encountered in patients who received the laser treatment. We concluded that pretreatment with He-Ne laser prior to FET may be an alternative choice for RIF-affected women; however, additional well-designed prospective studies are necessary to determine the precise clinical value of this treatment.
Assuntos
Aborto Habitual/radioterapia , Transferência Embrionária , Endométrio/efeitos da radiação , Lasers de Gás/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Aborto Habitual/terapia , Adulto , Blastocisto , Terapia Combinada , Implantação do Embrião/fisiologia , Implantação do Embrião/efeitos da radiação , Transferência Embrionária/métodos , Endométrio/irrigação sanguínea , Feminino , Congelamento , Humanos , Infertilidade Feminina/radioterapia , Infertilidade Feminina/terapia , Gravidez , Taxa de Gravidez , Resultado do TratamentoRESUMO
Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5-10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5-15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30-90% and final pregnancy rates of 13-88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of "toxic" follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the "hypothalamus-pituitary-ovary" axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.
Assuntos
Infertilidade Feminina/prevenção & controle , Laparoscopia/métodos , Ovário/cirurgia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/cirurgia , Feminino , Humanos , Síndrome do Ovário Policístico/patologia , Gravidez , Resultado da Gravidez , Taxa de GravidezRESUMO
Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients' survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.
Assuntos
Adenocarcinoma de Células Claras/genética , Complemento C3a/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Ovarianas/genética , Receptores de Complemento/genética , Adenocarcinoma de Células Claras/imunologia , Adenocarcinoma de Células Claras/mortalidade , Estudos de Casos e Controles , Complemento C3a/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Aprendizado de Máquina , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Receptores de Complemento/metabolismo , Análise de SobrevidaRESUMO
Endometriosis is a multifactorial inflammatory disease with persistent activation of the nuclear factor-κB (NF-κB) signalling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism of ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen, is able to activate focal adhesion kinase to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt-NF-κB signalling pathway, and its expression level correlates positively with that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo investigation further showed that DcR3 promoted the growth and spread of endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations are in support of DcR3 playing a critical role in the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a promising approach for the treatment of endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Adesão Celular , Endometriose/metabolismo , Endométrio/metabolismo , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Modelos Animais de Doenças , Progressão da Doença , Endometriose/patologia , Endometriose/fisiopatologia , Endometriose/cirurgia , Endométrio/patologia , Endométrio/fisiopatologia , Endométrio/cirurgia , Feminino , Xenoenxertos , Humanos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Transdução de SinaisRESUMO
STUDY OBJECTIVE: Previous studies suggest female-to-male transgender men tend to choose less invasive procedures, but the superior route of hysterectomy for them remains undetermined. DESIGN: A retrospective study (Canadian Task Force Classification II-3). SETTING: An academic tertiary hospital. PATIENTS: Fifty-six female-to-male transsexuals received total vaginal hysterectomy (VH) with bilateral salpingo-oophorectomy (BSO) between April 2008 and August 2016 at Taipei Veterans General Hospital, Taipei, Taiwan. INTERVENTIONS: The patients underwent natural orifice transluminal endoscopic surgery (NOTES) (n = 14) or the conventional approach (n = 42). MEASUREMENTS AND MAIN RESULTS: Medical charts and surgical records were reviewed retrospectively. The general characteristics of the patients were similar in both groups. There were no statistically significant differences in operative time, estimated blood loss, intraoperative and immediate postoperative complications, or length of hospital stay between the 2 groups. However, postoperative pain was significantly reduced in the NOTES group compared with the conventional group as evidenced by lower mean scores on the visual analog scale (4.9 ± 3.0 vs 7.1 ± 1.4 at 2 hours, p = .008; 1.5 ± 1.2 vs 3.0 ± 1.7 at 48 hours, p = .001; and 1.7 ± 1.0 vs 2.7 ± 1.1 at 72 hours, p < .001) and a lower mean accumulated dose of postoperative analgesics (38.9 ± 49.2 mg vs 88.8 ± 82.3 mg meperidine hydrochloride, p = .037). Analysis of variance with repeated measures with a Greenhouse-Geisser correction also showed that the mean scores for wound pain were statistically lower in the NOTES group (p < .001). There was no significant difference in the complication rate between the NOTES and conventional groups (7% vs 12%, p = .618). There were no severe complications, including infection episodes or internal bleeding events, within the NOTES group. CONCLUSION: NOTES VH with BSO in female-to-male transgender men significantly decreases postoperative pain and analgesic use. NOTES in female-to-male sex reassignment surgery provides a novel choice for transgender men, with equivalent safety compared with VH.
Assuntos
Histerectomia/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Salpingo-Ooforectomia/métodos , Pessoas Transgênero , Adulto , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Dor Pós-Operatória , Complicações Pós-Operatórias , Estudos Retrospectivos , TaiwanRESUMO
BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant for in vitro fertilization (IVF) cycles in poor ovarian responders (PORs). Several studies showed that DHEA supplementation could improve IVF outcomes of PORs. However, most of the PORs do not respond to DHEA clinically. Therefore, the aim of this study is to confirm the beneficial effects of DHEA on IVF outcomes of PORs and to investigate which subgroups of PORs can best benefit from DHEA supplementation. METHODS: This retrospective cohort study was performed between January 2015 and December 2017. A total of 151 PORs who fulfilled the Bologna criteria and underwent IVF cycles with the gonadotropin-releasing hormone antagonist protocol were identified. The study group (n = 67) received 90 mg of DHEA daily for an average of 3 months before the IVF cycles. The control group (n = 84) underwent the IVF cycles without DHEA pretreatment. The basic and cycle characteristics and IVF outcomes between the two groups were compared using independent t-tests, Chi-Square tests and binary logistic regression. RESULTS: The study and control groups did not show significant differences in terms of basic characteristics. The study group demonstrated a significantly greater number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality embryos at day 3 and a higher clinical pregnancy rate, ongoing pregnancy rate and live birth rate than those measures in the control group. The multivariate analysis revealed that DHEA supplementation was positively associated with clinical pregnancy rate (OR = 4.93, 95% CI 1.68-14.43, p = 0.004). Additionally, in the study group, the multivariate analysis showed that serum dehydroepiandrosterone-sulfate (DHEA-S) levels < 180 µg/dl were significantly associated with a rate of retrieved oocytes > 3 (OR = 5.92, 95% CI 1.48-23.26, p = 0.012). CONCLUSIONS: DHEA supplementation improves IVF outcomes of PORs. In PORs with DHEA pretreatment, women with lower DHEA-S level may have greater possibility of attaining more than 3 oocytes.
Assuntos
Desidroepiandrosterona/uso terapêutico , Fertilização in vitro , Adulto , Feminino , Humanos , Modelos Logísticos , Análise Multivariada , Recuperação de Oócitos , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: EpCAM is a transmembrane glycoprotein that functions as an epithelial marker in endometrial tissues. However, the correlation between EpCAM and endometrial carcinoma (EC) is not clear. METHODS: This study investigated the association between EpCAM and EC. Immunohistochemistry staining and bioinformatics analysis disclosed the clinical importance of low EpCAM expression. The migratory ability of cells expressing low EpCAM levels was studied in transwell invasion assays in vitro and an orthotopic intra-uterine tumor injection model in vivo. The Connectivity MAP was used to identify drugs that effectively inhibit cells with low EpCAM expression. RESULTS: According to immunohistochemistry analysis results, low EpCAM expression was associated with an advanced stage and lymph node metastasis in patients with endometrioid EC, and high EpCAM expression favored survival. EpCAM silencing promoted cell invasion, and EpCAM re-expression in EpCAM-silenced EC cells attenuated their invasiveness. EpCAM suppression in an orthotopic uterine implantation model promoted the lymph node metastasis of EC cells. According to quantitative PCR and promoter reporter analyses, estrogen receptor alpha signaling regulated EpCAM expression by enhancing its promoter activity. As shown in the Connectivity MAP analysis, transamin inhibited the invasiveness of EpCAM-silenced EC cells. CONCLUSIONS: The loss of EpCAM may increase the malignancy of EC, and these findings provide new insights into the prognostic role of EpCAM in patients with EC.
Assuntos
Neoplasias do Endométrio/etiologia , Molécula de Adesão da Célula Epitelial/fisiologia , Animais , Antifibrinolíticos/farmacologia , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo/fisiologia , Molécula de Adesão da Célula Epitelial/antagonistas & inibidores , Molécula de Adesão da Célula Epitelial/metabolismo , Receptor alfa de Estrogênio/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Inativação Gênica/fisiologia , Humanos , Estimativa de Kaplan-Meier , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias/métodos , Prognóstico , Transdução de Sinais/fisiologia , Ácido Tranexâmico/farmacologia , Transplante HeterólogoRESUMO
PURPOSE: To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. METHODS: A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. RESULTS: Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. CONCLUSION: Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.
Assuntos
Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/uso terapêutico , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/agonistas , Antagonistas de Hormônios/administração & dosagem , Oogênese/efeitos dos fármacos , Indução da Ovulação/métodos , Injeções de Esperma Intracitoplásmicas , Feminino , Humanos , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Serous carcinoma (SC) is the most common and lethal subtype of epithelial ovarian carcinoma; immunotherapy is a potential treatment for SC, however, the global immunological functions of SC as well as their change during the progression of SC have not been investigated in detail till now. We conducted a genome-wide integrative analysis to investigate the immunofunctionomes of SC at four tumor stages by quantifying the immunological functions defined by the Gene Ontology gene sets. DNA microarray gene expression profiles of 1100 SCs and 136 normal ovarian tissue controls were downloaded from the Gene Expression Omnibus database and converted to the functionome. Then the immunofunctionomes were reconstructed by extracting the offspring from the functionome for the four SC staging groups. The key immunological functions extracted from immunofunctionomes with a series of filters revealed that the immunopathy of SC consisted of a group of deregulated functions with the core members including B cell activation and differentiation, regulation of leukocyte chemotaxis/cellular extravasation, antigen receptor mediated signaling pathway, T helper mediated immunity and macrophage activation; and the auxiliary elements included leukocyte mediated immunity, regulation of inflammatory response, T cell differentiation, mononuclear cell migration, megakaryocyte differentiation, complement activation and cytokine production. These deregulated immunological functions reveal the candidates to target in the immunotherapy.