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BACKGROUND: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen. METHODS: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years. RESULTS: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT. CONCLUSION: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.
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Personas Transgénero , Adulto , Femenino , Humanos , Masculino , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Pueblo Asiatico , Glucemia/metabolismo , Distribución de la Grasa Corporal , Índice de Masa Corporal , Estudios de Casos y Controles , China/epidemiología , Pueblos del Este de Asia , Estrógenos/sangre , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Obesidad/sangre , Estudios Retrospectivos , Procedimientos de Reasignación de Sexo , Transexualidad/tratamiento farmacológico , Transexualidad/sangreRESUMEN
Primary mucinous ovarian carcinoma (PMOC) is a rare tumor, accounting for approximately 3% of all epithelial ovarian cancers (EOCs), with clinical risk factors and biologic features distinct from that of EOC. The prognosis for women with recurrent and high-grade PMOC remains poor, likely related to a poor response to conventional chemotherapy for EOC. A 27-year-old Chinese woman sought medical attention in January 2021 for abdominal distention from a large pelvic mass. After extensive investigations and workup, she was diagnosed with PMOC of the right ovary. Following multidisciplinary team (MDT) discussions, the patient underwent fertility-sparing surgery (FSS) (abdominal left adnexectomy, right partial oophorectomy, pelvic lymph node dissection, para-aortic lymph node dissection, omentectomy) as she yearned to preserve her fertility and the contralateral ovary appeared normal. Deep genetic analyses revealed ERBB2 co-amplification with CDK12 and chromosome 11q13.3 amplicon. Treatment with fertility-sparing surgery and adjuvant chemotherapy with trastuzumab results in complete remission. This novel strategy utilizing precise diagnostics and characterization of the histo-type of rare tumors allowed personalized targeting with optimum drug response for women who yearn fertility preservation and remission from the disease, especially when there is very limited clinical experience on management of such rare ovarian tumors.
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Preservación de la Fertilidad , Neoplasias Ováricas , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Adulto , Quimioterapia Adyuvante , Trastuzumab/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Preservación de la Fertilidad/métodos , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/tratamiento farmacológico , Adenocarcinoma Mucinoso/cirugía , Cromosomas Humanos Par 11/genética , Antineoplásicos Inmunológicos/uso terapéutico , Respuesta Patológica Completa , Quinasas Ciclina-DependientesRESUMEN
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
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Pyroptosis is a newly identified form of cell death, morphologically characterized by excessive cell swelling. In the present study, paclitaxel (PTX) combined with platinum were used as firstline chemotherapy, against ovarian cancer cells by inducing multiple types of cell death. However, it remains unclear whether PTX can induce pyroptosis in ovarian cancer cells. It was recently reported that PTX inhibited chloride channels, an inhibition known to cause cell swelling. In the present study, it was first verified that pyroptosislike cell death, as well as cleavedcaspase3 and cleavedgasdermin E (GSDME) were induced by PTX in A2780 ovarian cancer cells. PTX inhibited the background and hypotonicityactivated chloride currents, promoted intracellular chloride ion accumulation, those manifestations are similar to those of the classic volumeregulatory anion channel (VRAC) blocker, 4(2butyl6,7dichloro2cy-clopentylindan1on5yl) oxobutyric acid (DCPIB). Of note, both DCPIB and the downregulation of VRAC constituent protein leucinerich repeatcontaining 8a themselves could not induce persisted cell swelling and pyroptosislike phenotypes. However, they could enhance the effects of PTX in inducing pyroptosislike phenotypes, such as marked cell swelling, cell membrane rupture and excessive activation of caspase3 and GSDME Nterminal fragment, which ultimately caused marked pyroptosis in A2780 cells. These findings revealed a potential mechanism of PTX and offered new insights into the effects of a synergistical combination of PTX and VRACs blockers in ovarian cancer chemotherapy.
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Neoplasias Ováricas , Paclitaxel , Humanos , Femenino , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Piroptosis , Caspasa 3/metabolismo , Leucina/farmacología , Leucina/uso terapéutico , Canales de Cloruro , Línea Celular Tumoral , Cloruros/metabolismo , Cloruros/uso terapéuticoRESUMEN
The rapid recovery of gastrointestinal transit is critical for clinical recovery following laparoscopic procedures, including gynecological laparoscopies (GLs). Rehabilitation interventions post-surgery may provide significant prevention against early post-operative gastrointestinal motility disorders and maid aid in the acceleration of post-operative recovery in patients undergoing GLs. Among others, low-frequency electrical stimulation (LFES) has been demonstrated to pronouncedly mitigate the symptoms caused by gastrointestinal motility disorders; thus, this has attracted increasing attention over the past decade. The present study aimed to present an overview of the efficacy and application of LFES in gastrointestinal motility recovery following GL procedures.
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Ovarian cancer (OC) is the most lethal of all gynecologic malignancies with poor survival rates. Although surgical treatment and chemotherapy had advanced to improve survival, platinum-based chemoresistance remains a major hurdle in the clinical treatment of OC. The search for novel active ingredients for the treatment of drug-resistant OC is urgently needed. Here, we demonstrated that icaritin, the main active ingredient derived from the traditional Chinese herb Epimedium genus, significantly suppressed the proliferation, migration, and invasion of both drug-susceptible and cisplatin-resistant OC cells in vitro. Mechanistically, icaritin at 20 µM significantly inhibited the phosphorylation of Akt and mTOR, as well as decreased the expression of vimentin and increased the expression of E-cadherin. Our data indicate that icaritin, a prenylated flavonoid natural product, could serve as a potential inhibitor of cisplatin-resistant OC by inhibiting the Akt/mTOR signaling pathway.
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The vaginal microbiota, dominated by Lactobacilli, plays an important role in maintaining women's health. Disturbance of the vaginal microbiota allows infection by various pathogens such as Gardnerella spp. (GS) and related anaerobic bacteria resulting in bacterial vaginosis (BV). At present, the treatment options for BV are extremely limited. Treatment of antibacterial drugs and vaginal acidification are the two primary therapeutic methods. Acid electrolyzed water (AEW) is known to inactivate microorganisms and is considered a medical application in recent years. Studies have found that Lactobacillus acidophilus (LA) probiotics helps to inhibit GS-induced BV. Our study took GS and LA as the research object, which aims to explore AEW as a potential alternative therapy for BV and its underlying mechanisms. We first obtained the pH of AEW (3.71-4.22) close to normal vaginal pH (3.8-4.5) to maintain normal vaginal acidification conditions. Plate counting experiments showed that AEW (pH: 4.07, ORP: 890.67, ACC: 20 ppm) (20 ppm) could better inhibit the viability of GS but had a more negligible effect on LA. Then, we preliminarily explored the possible mechanism of AEW anti-GS using cell biology experiments and transmission electron microscopy. Results showed that the membrane permeability was significantly increased and the integrity of cell membrane was destroyed by AEW in GS than those in LA. AEW also caused protein leakage and cell lysis in GS without affecting LA. Meanwhile, AEW induced a number of reactive oxygen species (ROS) production in GS, with no obvious LA changes. Finally, we found that 20 ppm AEW exhibited excellent antibacterial effect on the vaginal secretions of women diagnosed with BV by Amsel criteria and sialic acid plum method. Taken together, our findings manifest that 20 ppm AEW has an excellent antibacterial effect in GS with less effect on LA, which might be expected to become a potential therapy for BV.
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Epithelial ovarian cancers (EOC) present as malignant tumors with high mortality in the female reproductive system diseases. Acquired resistance to paclitaxel (PTX), one of the first-line treatment of EOC, remains a therapeutic challenge. ClC-3, a member of the voltage-gated Cl- channels, plays an essential role in a variety of cellular activities, including chemotherapeutic resistance. Here, we demonstrated that the protein expression and channel function of ClC-3 was upregulated in PTX resistance A2780/PTX cells compared with its parental A2780 cells. The silence of ClC-3 expression by siRNA in A2780/PTX cells partly recovered the PTX sensitivity through restored the G2/M arrest and resumed the chloride channel blocked. ClC-3 siRNA both inhibited the expression of ClC-3 and ß-tubulin, whereas the ß-tubulin siRNA reduced the expression of itself only, without affecting the expression of ClC-3. Moreover, treatment of ClC-3 siRNA in A2780/PTX cells increased the polymerization ratio of ß-tubulin, and the possibility of proteins interaction between ClC-3 and ß-tubulin was existing. Take together, the over-expression of ClC-3 protein in PTX-resistance ovarian cancer cells promotes the combination of ClC-3 and ß-tubulin, which in turn increase the ration of free form and decrease the quota of the polymeric form of ß-tubulin, and finally reduce the sensitivity to PTX. Our findings elucidated a novel function of ClC-3 in regulating PTX resistance and ClC-3 could serve as a potential target to overcome the PTX resistance ovarian cancer.
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Canales de Cloruro/biosíntesis , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacología , Moduladores de Tubulina/metabolismo , Tubulina (Proteína)/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Canales de Cloruro/química , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/fisiología , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Polimerizacion/efectos de los fármacos , Estructura Secundaria de Proteína , Estructura Terciaria de ProteínaRESUMEN
Fibroblast growth factor receptors (FGFRs) have been implicated in the malignant transformation and chemoresistance of epithelial ovarian cancer; however, the underlying molecular mechanisms are poorly understood. Increased sialyltransferase activity that enhances protein sialylation is an important posttranslational process promoting cancer progression and malignancy. In the present study, α2,6sialyltransferase (ST6GalI) overexpression or knockdown cell lines were developed, and FGFR1 was examined to understand the effect of sialylation on migration and drug resistance, and the underlying mechanisms. It was identified that cells with ST6GalI overexpression had increased cell viability and migratory ability upon serum deprivation. Moreover, ST6GalI overexpression cells had strong resistance to paclitaxel, as demonstrated by low growth inhibition rate and cell apoptosis level. A mechanistic study showed that ST6GalI overexpression induced high α2,6sialylation of FGFR1 and increased the expression of phosphoERK1/2 and phosphofocal adhesion kinase. Further study demonstrated that the FGFR1 inhibitor PD173047 reduced cell viability and induced apoptosis; however, ST6GalI overexpression decreased the anticancer effect of PD173047. In addition, ST6GalI overexpression attenuated the effect of Adriamycin on cancer cells. Collectively, these results suggested that FGFR1 sialylation plays an important role in cell migration and drug chemoresistance in ovarian cancer cells.
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Antígenos CD/metabolismo , Antineoplásicos/farmacología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Resistencia a Antineoplásicos , Neoplasias Ováricas/tratamiento farmacológico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Sialiltransferasas/metabolismo , Antígenos CD/genética , Apoptosis , Biomarcadores/análisis , Línea Celular Tumoral , Movimiento Celular , Supervivencia Celular , Femenino , Quinasa 1 de Adhesión Focal/genética , Quinasa 1 de Adhesión Focal/metabolismo , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Paclitaxel/farmacología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Sialiltransferasas/genética , Transducción de SeñalRESUMEN
Comparison of the fluorescence intensity caused by the accumulation of PpIX in endometrial cancer xenografts in nude mice after low-dose 5-Aminolevulinic acid (ALA) injection combined with siRNA transfection was mediated by ultrasound microbubbles and polyethyleneimine (PEI) to explore the feasibility of the ultrasound microbubble technique as transfection agents. Knockdown of ferrochelatase (FECH) in human endometrial cancer xenografts in nude mice was performed by transfection with FECH-siRNA mediated by PEI and ultrasound microbubbles alone or in combination; then, low-dose ALA was injected. Subsequently, an in vivo animal imaging system was employed to detect the fluorescence intensity in xenografts. Red fluorescence was observed in xenografts given more than 6.25 mg kg-1 of ALA. When the dose of ALA was greater than 50 mg kg-1 , there was a significant difference in the fluorescence between tumor and other tissues. After the nude mice were transfected with siRNA and treated with low-dose ALA (1.0 mg kg-1 ), apparent PpIX fluorescence of the xenografts was observed, and the fluorescence intensity was PEI+ ultrasound microbubbles > PEI > ultrasound microbubbles. Ultrasound microbubbles in combination with PEI could generate a higher fluorescence intensity of PpIX than that obtained with ultrasound microbubbles or PEI alone, and ultrasound microbubbles could wholly or partially replace PEI under certain conditions.
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Ácido Aminolevulínico/farmacología , Ferroquelatasa/metabolismo , Microburbujas , Polietileneimina , ARN Interferente Pequeño , Ácido Aminolevulínico/administración & dosificación , Ácido Aminolevulínico/química , Animales , Línea Celular Tumoral , Neoplasias Endometriales , Femenino , Ferroquelatasa/química , Humanos , Ratones , Ratones Desnudos , Neoplasias Experimentales , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/farmacología , Protoporfirinas , Ultrasonido , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIMS: Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers. Currently, the first-line OC treatment consists of cytoreductive surgery and platinum-based chemotherapy. However, most patients develop chemoresistance after the first-line treatment limits the success of treatment. Therefore, there is an urgent need to identify effective therapeutic agents. MAIN METHODS: Cell viabilities were detected by MTS assay; Annexin V-FITC/PI assay and western blotting assay were performed to analyze the apoptotic cells in vitro; An immunofluorescence assay was performed to analyze the TUNEL+ apoptotic cells in vivo; Patient-derived xenografts were established to test the in vivo antitumor effects; The key proteins of p53, caspase-mediated apoptotic pathway and Akt/mTOR pathway were detected by Western blotting. KEY FINDINGS: Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited the proliferation of drug-sensitive OC cells (OV2008 and C13*) and cisplatin resistant OC cells A2780cp. Icaritin induced OC cell apoptosis in vitro, as indicated by the increase of Annexin V+/PI+ apoptotic cells analyzed with flow cytometry, and the cleavage of caspase 9, caspase 3 and poly-ADP-ribose polymerase (PARP) detected with western blotting. Icaritin also inhibited tumor growth and induced OC cells apoptosis in patient-derived xenografts, as indicated by the tumor growth delay and increase of TUNEL-positive cells in tumor tissues. The icaritin-induced OC cell apoptosis may be associated with the activation of p53 and the suppression of Akt/mTOR pathway. SIGNIFICANCE: This study sheds light on the underlying mechanisms of antitumor effect of icaritin, and warrants clinical trial for treatment of OC.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Flavonoides/farmacología , Proteína Oncogénica v-akt/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Fragmentos de Péptidos/agonistas , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/agonistas , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Ratones , Ratones Desnudos , Ratones SCID , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cisplatin (DDP) is currently one of the most commonly used chemotherapeutic drugs for treating ovarian and lung cancer. However, resistance to cisplatin is common and it often leads to therapy failure. In addition, the precise mechanism of cisplatin resistance is still in its infancy. In this study, we demonstrated that the oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase (6PGD) promotes cisplatin resistance. We showed that cisplatin-resistant cancer cells (C13∗ and A549DDP), had higher levels of 6PGD compared to their cisplatin-sensitive counterparts (OV2008 and A549). Furthermore, ovarian and lung cancer patients with higher 6PGD levels have worse survival outcomes relative to patients with lower 6PGD expression. Interestingly, we found that the upregulation of 6PGD in cisplatin-resistant cells was due to the decreased expression of miR-206 and miR-613, which we found to target this enzyme. We further demonstrate that suppressing 6PGD using shRNA, inhibitor or miR-206/miR-613, either as single agents or in combination, could sensitize cisplatin-resistant cancer cells to cisplatin treatment and thereby improving the therapeutic efficacy of cisplatin. Taken together, our results suggest that 6PGD serves as a novel potential target to overcome cisplatin resistance.
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OBJECTIVE: To assess the efficacy of uterine artery embolization (UAE) combined with dilation and curettage (D&C) within 24 hours for the treatment of a cesarean scar pregnancy (CSP), compared with methotrexate and D&C. METHODS: A retrospective cohort study of 119 women with CSP was conducted at two tertiary hospitals in Guangzhou and Shenzhen, China, during 2009-2012. Twenty-six women received systemic methotrexate followed by D&C, and 93 women were treated with UAE followed by D&C within 24 hours. RESULTS: Mean blood loss was 261.0±357.4 mL in the methotrexate group versus 14.1±40.6 mL in the UAE group (P<0.001). The time to resolution of the level of ß-human chorionic gonadotropin was 40.5±17.2 days versus 15.4±7.7 days (P<0.001), respectively. The duration of hospitalization was 14.6±9.2 days versus 6.2±3.7 days (P<0.001), respectively. An additional intervention was needed in 9 (35%) women in the methotrexate group and in 5 (5%) in the UAE group (P<0.001). CONCLUSION: UAE combined with D&C within 24 hours was an effective uterine preservation treatment for CSP, and was associated with less blood loss and a shorter hospital stay than administration of methotrexate followed by D&C.