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1.
Medicine (Baltimore) ; 99(1): e18447, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895773

RESUMO

Prenatal examination is a pivotal measure to prevent high-risk pregnancy and to ensure the safety of both mother and infant. However, pregnant women in Linzhi Prefecture in the Tibet Autonomous Region (TAR) often cannot obtain regular prenatal examinations due to limited accessibility of healthcare facilities, shortage of medical staff, and lack of medical equipment. Health education is an important approach to solve this ever-growing issue of pregnant women in rural Tibet.To evaluate the efficacy of flexible methods of health education programs on improving compliance among pregnant women from Tibet, China.In May to November of 2018, a total of 168 pregnant women receiving prenatal examination in a tertiary referral hospital in Linzhi Prefecture were recruited and randomly assigned to a control (n = 85) and intervention group (n = 83). All pregnant women were followed up until delivery. The pregnant women in the control group received regular prenatal examination and health education programs. Other than receiving routine prenatal care, participants of the interventional group also voluntarily joined the WeChat Social Messaging platform. Online resources posted by the maternity schools provided convenience and flexibility for the pregnant woman. The number of prenatal examinations was statistically significant between the 2 groups. The effect of flexible patterns of health education programs on improving the compliance of pregnant women in Tibet was assessed.The number of prenatal examinations in the intervention group was 2.646 times, which was higher than that in the control group (P < .01). Multivariate analysis demonstrated that interventional measures and ethnicity were the influencing factors of the number of prenatal examinations for pregnant women in Linzhi after the adjustment of age, history of adverse pregnancy, education level, ethnicity, multiparity, gestational complications, and medical history. The number of prenatal examinations for the pregnant Tibetan women was 0.535 times lower compared with that of the pregnant Han women (95% CI: -0.089, 1.157, P = .091).Flexible forms of health education during the antenatal period can effectively increase the compliance of pregnant women in Tibet.


Assuntos
Educação em Saúde/métodos , Cooperação do Paciente , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Feminino , Humanos , Gravidez , Rede Social , Tibet
2.
Cancer Biomark ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31771040

RESUMO

BACKGROUND: The current cervical cancer screening strategies based on Papanicolaou (Pap) and Human papillomavirus (HPV) tests receive great achievement but still exhibit many limitations in clinical practice. Exploring new biomarkers as stratified management method in HPV primary screening is becoming the tendency of current research. METHODS: Immunocytochemistry (ICC) of FHIT and C-MYC were performed on exfoliated cervical cells from 197 eligible high-risk HPV positive women. Mann-Whitney U test, Pearson Chi-Square test, logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the diagnostic efficiency. RESULTS: ICC staining intensity of FHIT and C-MYC in high-grade cervical intraepithelial neoplasia (CIN) specimens was significantly different from low-grade CIN and normal specimens. Compared with Pap test, ROC analysis of ICC in detecting high-grade CIN resulted in a larger area under the curve (AUC) (0.805 and 0.814 vs 0.723, p< 0.001). FHIT achieved higher sensitivity than Pap test (79.41% vs 66.67%, p= 0.04). Logistic regression analysis of the combination of two biomarkers led to higher AUC value, specificity and PPV than any single biomarker. CONCLUSIONS: The utility of FHIT and C-MYC ICC analysis in cervical exfoliated cells of HPV-positive women displayed superior diagnostic potential and may improve clinical performance of cervical cancer screening.

3.
Ther Adv Med Oncol ; 11: 1758835919874649, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632465

RESUMO

Background: A review of the evidence has indicated the critical role of long noncoding RNA (lncRNA) LSINCT5 in a large number of human cancers. However, the mechanistic involvement of LSINCT5 in endometrial carcinoma (EC) is still unknown. Here the authors aim to characterize the expression status of LSINCT5 and elucidate its mechanistic relevance to EC. Methods: Relative expression of LSINCT5 and HMGA2 were quantified by a real-time polymerase chain reaction. SiRNAs were employed to specifically knockdown endogenous LSINCT5 in EC cells. Cell proliferation was measured with Cell Count Kit-8 kit (CCK-8, Dojindo, Kumamoto, Japan) and cell growth was assessed by a colony formation assay. The cell cycle was analyzed with propidium iodide (PI) staining. Apoptotic cells were determined by flow cytometry after Annexin V/PI double-staining. Cell migration was evaluated by a wound-healing assay, and cell invasion was assessed using a transwell migration assay. The protein levels of HMGA2, Wnt3a, p-ß-catenin, c-myc, ß-actin, and GAPDH were determined by western blot. Results: The authors observed positively correlated and aberrantly up-regulated LSINCT5 and HMGA2 in EC. LSINCT5 deficiency significantly inhibited cell proliferation, cell cycle progression, and induced apoptosis. Meanwhile, cell migration and invasion were greatly compromised by the LSINCT5 knockdown. LSINCT5 stabilized HMGA2, which subsequently stimulated activation of Wnt/ß-catenin signaling and consequently contributed to the oncogenic properties of LSINCT5 in EC. Conclusions: Our data uncovered the oncogenic activities and highlighted the mechanistic contributions of the LSINCT5-HMGA2-Wnt/ß-catenin signaling pathway in EC.

4.
J Cancer ; 10(20): 4954-4960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598168

RESUMO

Background: Endometrial cancer is the most common gynecologic malignancy in women in the developed countries. Despite recent progress in functional characterization of voltage-gated sodium channel (Nav) in multiple cancers, very little was known about the expression of Nav in human endometrial cancer. The present study sought to determine the role of Nav and molecular nature of this channel in the endometrial cancer. Methods: PCR approach was introduced to determine expression level of Nav subunits in endometrial cancer specimens. Pharmacological agents were used to investigate Nav function in endometrial cancer cells. Flow cytometry were used to test cancer apoptosis, and invasion assays were applied to test tumor metastasis. Results: Transcriptional levels of the all Nav α and ß subunits were determined by real time-PCR in endometrial cancer with pair tissues of carcinoma and adjacent nonneoplastic tissue, Nav1.7 was the most highly expressed Nav subtype in endometrial cancer tissues. Nav1.7 level was closely associated with tumor size, local lymph node metastasis, and 5-year and 10-year survival ratio. Inhibition of this channel by Nav1.7 blocker PF-05089771, promoted cancer apoptosis and attenuated cancer cell invasion. Conclusion: These results establish a relationship between voltage-gated sodium channel protein and endometrial cancer, and suggest that Nav1.7 is a potential prognostic biomarker and could serve as a novel therapeutic target for endometrial cancer.

5.
Am J Obstet Gynecol ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31586602

RESUMO

BACKGROUND: Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. OBJECTIVE: The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. STUDY DESIGN: The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. RESULTS: Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). CONCLUSION: For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31517308

RESUMO

Objective: The aims of this study were to assess the role of omentectomy in the staging of uterine serous carcinoma (USC) and to evaluate its impact on patient outcomes. Study design: Patients diagnosed with USC at the First Affiliated Hospital of Sun Yat-sen University of China were retrospectively reviewed. The clinicopathological characteristics and survival data of 187 patients were analyzed. Risk factors for omental metastasis were evaluated. Kaplan-Meier survival curves were used to compare survival status and the presence of omental metastasis. Results: We found that 35 of 187 patients (18.7%) had omental metastases. Omental metastasis was significantly associated with adnexal involvement (40.0% vs 19.1%, P = 0.008, OR 2.828, 95% CI 1.286-6.218). Multivariate analysis showed that in addition to lymph node metastases and suboptimal surgery, omental metastasis in USC remained an independent predictor of decreased PFS and OS (PFS, HR 1.48, 95% CI 1.14-4.63, P = 0.024; OS, HR 1.39, 95% CI 1.04-3.60, P = 0.043). Conclusions: The incidence of omental metastasis is not low in patients with USC. Visual assessment and omental biopsy may be insufficient for recognizing occult metastases. Omentectomy should be part of the staging surgery in USC patients because it provides additional information about survival. Prospective studies are needed to confirm these results.

7.
Carcinogenesis ; 40(10): 1220-1228, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31102403

RESUMO

From initial human papillomavirus (HPV) infection and precursor stages, the development of cervical cancer takes decades. High-sensitivity HPV DNA testing is currently recommended as primary screening method for cervical cancer, whereas better triage methodologies are encouraged to provide accurate risk management for HPV-positive women. Given that virus-driven genomic variation accumulates during cervical carcinogenesis, we designed a 39 Mb custom capture panel targeting 17 HPV types and 522 mutant genes related to cervical cancer. Using capture-based next-generation sequencing, HPV integration status, somatic mutation and copy number variation were analyzed on 34 paired samples, including 10 cases of HPV infection (HPV+), 10 cases of cervical intraepithelial neoplasia (CIN) grade and 14 cases of CIN2+ (CIN2: n = 1; CIN2-3: n = 3; CIN3: n = 9; squamous cell carcinoma: n = 1). Finally, the machine learning algorithm (Random Forest) was applied to build the risk stratification model for cervical precursor lesions based on CIN2+ enriched biomarkers. Generally, HPV integration events (11 in HPV+, 25 in CIN1 and 56 in CIN2+), non-synonymous mutations (2 in CIN1, 12 in CIN2+) and copy number variations (19.1 in HPV+, 29.4 in CIN1 and 127 in CIN2+) increased from HPV+ to CIN2+. Interestingly, 'common' deletion of mitochondrial chromosome was significantly observed in CIN2+ (P = 0.009). Together, CIN2+ enriched biomarkers, classified as HPV information, mutation, amplification, deletion and mitochondrial change, successfully predicted CIN2+ with average accuracy probability score of 0.814, and amplification and deletion ranked as the most important features. Our custom capture sequencing combined with machine learning method effectively stratified the risk of cervical lesions and provided valuable integrated triage strategies.

8.
Reprod Biomed Online ; 38(4): 549-559, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30772194

RESUMO

Endometriosis is a complex and heterogeneous disorder of unknown aetiology. This benign disease possesses special biological behaviours that mimic those of malignant tumours. A pro-endometriotic niche established by an existing lesion is a supportive micro-environment for the progression of endometriosis. After the accumulation of cells by an existing lesion, these components display distinct characteristics that impair immune surveillance. Subsequent retrograde menstruation of endometrial stromal cells into the pro-endometriotic niche facilitates endometriotic progression from early initiation to an advanced lesion. This study aimed to highlight the innovative role of the pro-endometriotic niche in endometriosis, and to provide valuable treatment targets for endometriosis.

9.
Reprod Biol Endocrinol ; 16(1): 122, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518376

RESUMO

Endometriosis is a complex and heterogeneous disorder with unknown etiology. Dysregulation of macrophages and innervation are important factors influencing the pathogenesis of endometriosis-associated pain. It is known to be an estrogen-dependent disease, estrogen can promote secretion of chemokines from peripheral nerves, enhancing the recruitment and polarization of macrophages in endometriotic tissue. Macrophages have a role in the expression of multiple nerve growth factors (NGF), which mediates the imbalance of neurogenesis in an estrogen-dependent manner. Under the influence of estrogen, co-existence of macrophages and nerves induces an innovative neuro-immune communication. Persistent stimulation by inflammatory cytokines from macrophages on nociceptors of peripheral nerves aggravates neuroinflammation through the release of inflammatory neurotransmitters. This neuro-immune interaction regulated by estrogen sensitizes peripheral nerves, leading to neuropathic pain in endometriosis. The aim of this review is to highlight the significance of estrogen in the interaction between macrophages and nerve fibers, and to suggest a potentially valuable therapeutic target for endometriosis-associated pain.


Assuntos
Endometriose/metabolismo , Estrogênios/metabolismo , Macrófagos/metabolismo , Fibras Nervosas/metabolismo , Citocinas/metabolismo , Endometriose/patologia , Feminino , Humanos
10.
J Cancer ; 9(21): 4087-4091, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410613

RESUMO

Neoadjuvant chemotherapy (NACT) plays an important role in ovarian cancer. The appropriate time interval from the completion of NACT to interval debulking surgery (TTS) in ovarian cancer is still unknown. The aim of this retrospective study was to evaluate the effect of the time interval between the end of NACT and surgery (TTS ≤ 4 weeks vs TTS > 4 weeks) on the survival outcomes among patients with advanced-stage ovarian, tubal, and peritoneal cancers. 152 patients with stage III or IV ovarian, tubal, and peritoneal cancers were included in this retrospective cohort study: 115 in the TTS ≤4 weeks and 37 in the TTS >4 weeks groups. The Kaplan-Meier analysis showed that the progression-free survival in the TTS ≤4 weeks group was longer than that in the TTS >4 weeks group (26 vs 14 months, P=0.04). However, the overall survival was not different between the two groups (66 vs 36 months, P=0.105). The multivariate analysis presented that delay in surgery after NACT (TTS >4 weeks) was associated with a shorter progression-free (P=0.002) but not overall survival (P=0.231). Our findings demonstrated no relationship between the NACT to surgery interval and OS, while a detrimental effect of TTS >4 weeks on PFS was observed.

11.
J Pain Res ; 11: 1999-2009, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310304

RESUMO

Purpose: Recent studies have shown that abnormal distribution of pelvic nerves contributes to endometriosis-associated pain. However, the relationship between neurogenesis and pain severity in endometriosis still remains uncertain, which makes it an enigma for both gynecologists as well as neuropathologists. In this study, we tried to explore a special phenomenon, perineural invasion (PNI), in deep infiltrating endometriosis (DIE) and investigated the correlation between PNI- and DIE-associated pain. Patients and methods: The study was conducted in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Sun Yat-sen University from June 2012 to January 2015. In total, 64 patients with DIE were enrolled. They received laparoscopically surgical resection of endometriotic lesions. The Kruskal-Wallis and Mann-Whitney tests were used for comparisons of enumeration data. Spearman rank correlation was used for linear analysis. Results: Immunohistochemical analysis demonstrated that PNI was commonly found in DIE lesions. Patients were divided into PNI (+) group and PNI (-) group. The visual analog scale scores of dysmenorrhea, dyspareunia, and chronic pelvic pain were higher in PNI (+) group than in PNI (-) group. Also, we found significantly increased density of newly formed nerve fibers as well as microvessels in lesions of PNI (+) group. Further, double immunofluorescence showed a closely spatial nerve-vessel network in the endometriotic lesion of PNI (+) group. More importantly, correlation analysis revealed positive relation between the density of newly formed nerve fibers in the lesion and the density of microvessels in lesions of PNI (+) group. Conclusion: This study suggests that PNI in endometriotic lesions plays an important role in endometriosis-associated pain, mainly through a mechanism named "neuroangiogenesis".

12.
Int J Oncol ; 53(2): 855-865, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901108

RESUMO

Activity of the voltage-gated Nav1.5 sodium channel has been reported to be involved in cell proliferation, cancer invasion and gene expression. In addition, eicosapentaenoic acid (EPA) has recently been suggested to inhibit ovarian cancer cell growth and suppress tumor metastasis. The present study aimed to explore the association between EPA, the Nav1.5 sodium channel and ovarian cancer cells. Using patch-clamp technique and RNA interference approaches, sodium currents were recorded in epithelial ovarian cancer cells, and it was confirmed that the Nav1.5 channel carried the sodium currents. Furthermore, EPA effectively inhibited sodium currents in a dose-dependent manner, shifted the steady-state inactivation curve of sodium currents to the hyperpolarizing direction and reduced sodium window currents. In addition, EPA induced a shift in the inactivation curve in a dose-dependent manner. Inhibition of the sodium channel, either by EPA or by Nav1.5 knockdown, attenuated ovarian cancer cell migration and proliferation. To the best of our knowledge, the present study is the first to conduct sodium current recording in ovarian cancer cells, and revealed that EPA may inhibit Nav1.5-mediated ovarian cancer cell migration and growth. These findings not only present a potential prognostic biomarker for ovarian cancer, but also provide a strategy towards the development of novel pharmacological treatments for patients with ovarian cancer.


Assuntos
Ácido Eicosapentaenoico/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Prognóstico
13.
Am J Transl Res ; 10(3): 684-695, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29636859

RESUMO

OBJECTIVE: The expression level and clinical significances of long non-coding RNAs (LncRNAs) are presently unknown in the early-stage cervical cancer (CC). This study was aimed to explore the expression signatures of lncRNAs between normal and cervix carcinoma tissues and the prognostic value of LncRNAs in early-stage CC patients. MATERIALS AND METHODS: The patients diagnosed with FIGO stage I-IIb CC of the First Affiliated Hospital of Sun Yat-sen University between January 1st 2006 and December 31st 2009 were retrospectively reviewed. Molecular microarray was conducted to identify differentially expression profiles of LncRNAs. In situ hybridization was applied for detection of candidate lncRNAs in cervical tissues. RESULTS: A total of 2574 upregulated lncRNAs and 3270 downregulated lncRNAs with significantly differential expression (≥2.0-fold) were identified. Among the differentially expressed lncRNAs, RP11-396F22.1 expression was one of the most significantly overexpressed in the CC tissues compared to nomal cervical tissues (P<0.001). In situ hybridization confirmed RP11-396F22.1 expression was highly expressed in cancerous tissues. The results of Scratch and Transwell test showed that the migration ability decreased remarkably in transfected group (P<0.001). Moreover, the coding gene cpne8 was significantly upregulated by RP11-396F22.1 knockdown (P=0.035). CONCLUSIONS: These findings demonstrate that LncRNA RP11-396F22.1 might be a potent biomarker for CC progression.

14.
Am J Transl Res ; 10(3): 866-874, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29636876

RESUMO

MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level and participate in various biological processes. Our previous studies suggested that miR-143-3p functions as a tumor suppressor and has a role in the progression of ovarian cancer, in part through the regulation of the tumor promoter. In this study, we found that the mRNA expression level of miR-143-3p was significantly decreased in ovarian cancer tissues, in comparison with normal ovarian tissues by high-throughput miRNA profiling and quantitative RT-PCR. Secondly, we indicated that the up-regulation of miR-143-3p in the ovarian cancer cell lines SKOV3, ES2, and OVCAR3 significantly reduced their proliferation, migration, and invasion. Furthermore, miR-143-3p inhibited the growth of ovarian tumors in vivo in a xenograft experiment. In addition, miR-143-3p down-regulated the expression of transforming growth factor (TGF)-ß-activated kinase 1 (TAK1) in human ovarian cancer cells. Therefore, our study indicates that miR-143-3p inhibited the proliferation, migration, and invasion of ovarian cancer cells in vitro, as well as ovarian tumorigenesis in vivo. This inhibitory effect may target TAK1, suggesting a potential application of the miR-143-3p-TAK1 pathway in the clinical diagnosis and treatment of ovarian cancer.

15.
Oncol Lett ; 15(4): 5584-5592, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29552195

RESUMO

Long non-coding RNAs (lncRNAs) have been acknowledged to serve a significant role in cancer biology and abnormal expression in tumors is frequently observed. However, their mechanisms in cervical cancer remain unclear. With a genome-wide analysis of lncRNA expression in cervical cancer tissues, the present study aimed to identify lncRNA targets for the further study of cervical cancer. To elucidate the specific role of lncRNAs in the pathogenesis of this type of cancer, 6 cervical cancer samples paired with normal cervical tissues were obtained. Expression profiles of lncRNAs and mRNAs were constructed through microarray analysis and confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methods. Gene Ontology and pathway enrichment analyses were performed with computational methods. On the basis of correlations between the differential expression levels of lncRNAs and mRNAs, a coding-non-coding gene co-expression network (CNC network) was established. The differential expression of 5,844 lncRNAs and 4,436 mRNAs were discovered in cervical cancer samples compared with normal cervical tissues. Among the differentially expressed lncRNAs, 14 were chosen at random and validated by RT-qPCR; the majority of the results measured were consistent with the microarray results. Furthermore, the lncRNA ENST00000551152 was found to be upregulated and TCO. NS_00001368 lncRNA was downregulated in cervical cancer cell lines. The CNC network included 592 network nodes and 934 associations between 12 lncRNAs and 580 protein-coding genes, indicating that one lncRNA could act on a maximum of 141 coding genes, and that one coding gene may corresponded with a maximum of 5 lncRNAs. Overall, the present study has provided a complete expression profile of lncRNAs and mRNAs in cervical cancer, which may now be used to establish a solid foundation for cervical cancer research. These results may provide significant information for improving the understanding of the pathogenesis of cervical cancer and indicate potential therapeutic targets.

16.
Oncol Lett ; 15(3): 3458-3463, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29456722

RESUMO

Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines. Results indicated that fucosterol exhibited selective inhibitory activity against human HeLa cervical cancer cell line with an IC50 of 40 µM. Fucosterol also induced apoptosis in HeLa cells and prompted reactive oxygen species mediated alterations in mitochondrial membrane potential. It triggered cell cycle arrest of HeLa cells at G2/M check point and exerted inhibitory effects on cell migration. The activation of the phosphoinositide-3-kinase (PI3K)/AKT Serine/Threonine Kinase 1 (AKT)/mechanistic target of Rapamycin (mTOR) pathway is important in cancer tumorigenesis, progression and chemotherapy resistance. The results demonstrated that fucosterol significantly inhibited the expression levels of key proteins of the PI3K/Akt/mTOR signaling pathway. Overall, the results of the present study suggest that fucosterol may prove beneficial in the management of cervical cancer.

17.
Int J Oncol ; 52(3): 815-827, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29393390

RESUMO

Chemotherapeutic resistance remains a critical clinical issue is responsible for treatment failure in patients with ovarian cancer. Evidence of the involvement of miRNAs in chemoresistance in ovarian cancer has been recently emerging. However, the underlying molecular links between chemoresistance and miRNAs remain largely unknown. In this study, we report that miR­149­5p expression is markedly elevated in chemoresistant ovarian cancer tissues compared with the chemosensitive ovarian cancer tissues. Furthermore, the silencing of miR­149­5p enhanced the chemosensitivity of ovarian cancer cells to cisplatin in vitro and in vivo. Conversely, the upregulation of miR­149­5p aggravated chemoresistance in ovarian cancer cells. Our results further revealed that miR­149­5p directly targeted the core kinase components of the Hippo signaling pathway, STE20-like kinase (MST)1 and protein salvador homolog 1 (SAV1), resulting in the inactivation of TEA domain (TEAD) transcription. On the whole, our findings reveal a novel mechanism of of action miR­149­5p in inducing chemotherapeutic resistance in ovarian cancer, indicating that miR­149­5p may serve as a chemotherapeutic response indicator and a potential therapeutic target in ovarian cancer.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genética , Apoptose/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Ovário/cirurgia , Proteínas Serina-Treonina Quinases/genética , Regulação para Cima
18.
J Minim Invasive Gynecol ; 25(5): 923-926, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29427779

RESUMO

A 23-year-old female patient with refractory chylous ascites was successfully treated with laparoscopic ligation of the ruptured lymphatic vessel. The young patient developed abdominal distention after right-side pelvic lymph node dissection for dysgerminoma of the right ovary. Conservative managements failed to control the symptoms. Laparoscopic surgery was performed after oral administration of peanut oil, revealing the presence of a whitish fluid in the abdominal cavity. The responsible lesion of the chylous ascites was detected in the right obturator fossa and ligated with the HEM-O-LOK System (Kangji Medical Instrument Co., Ltd., Hangzhou City, Zhejiang Province, China). The patient experienced an uneventful recovery and has been completely free of symptoms for 1 year. Laparoscopic surgery should be considered as a treatment of choice for intractable chylous ascites, and peanut oil could be used before surgery as an effective way to facilitate detection of the leakage during surgery.


Assuntos
Ascite Quilosa/cirurgia , Laparoscopia/métodos , Excisão de Linfonodo/efeitos adversos , Óleo de Amendoim/uso terapêutico , Ascite Quilosa/etiologia , Feminino , Humanos , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Adulto Jovem
19.
Biosci Rep ; 38(1)2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29101241

RESUMO

Long non-coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play crucial regulatory roles in many types of cancer. However, the biological function of long ncRNA (lncRNA) SNHG20 in ovarian cancer is still unclear. In the present study, we found that lncRNA SNHG20 was significantly increased in ovarian cancer. In addition, lncRNA SNHG20 knockdown suppressed the ovarian cancer progression, whereas overexpression of SNHG20 showed the opposite effects. Moreover, our results also revealed that lncRNA SNHG20 knockdown inhibited Wnt/ß-catenin signaling activity by suppressing ß-catenin expression and reversing the downstream target gene expression. Taken together, lncRNA SNHG20 plays an pivotal role in ovarian cancer progression by regulating Wnt/ß-catenin signaling.


Assuntos
Proliferação de Células/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , beta Catenina/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Cancer Res ; 78(4): 877-890, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29229603

RESUMO

Cancer spread to lymph nodes predicts poor survival but underlying mechanisms remain little understood. In this study, we show that overexpression of the long noncoding RNA LNMICC associates with lymph node metastasis of primary cervical cancer, where it serves as an independent high-risk factor in patient survival. Functional investigations demonstrated that LNMICC promoted lymph node metastasis by reprogramming fatty acid metabolism, by recruiting the nuclear factor NPM1 to the promoter of the fatty acid binding protein FABP5. We also found that the prometastatic effects of LNMICC were directly targeted and suppressed by miR-190. Our results establish a new mechanism of lymph node metastasis and highlight LNMICC as a candidate prognostic biomarker and therapeutic target in cervical cancer.Significance: These results establish the role of a novel long noncoding RNA in lymph node metastasis, with implications as a candidate prognostic biomarker and therapeutic target in cervical cancer. Cancer Res; 78(4); 877-90. ©2017 AACR.


Assuntos
Ácidos Graxos/metabolismo , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Feminino , Humanos , Metástase Linfática , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/patologia
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