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1.
EBioMedicine ; 104: 105155, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38744109

RESUMO

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

2.
Am J Transl Res ; 16(3): 855-863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586092

RESUMO

OBJECTIVE: To determine the effects of multidisciplinary team (MDT) nursing mode on the swallowing function and oral hygiene in patients after radical resection of tongue cancer (TC). METHODS: The data of 88 patients with TC treated in West China School/Hospital of Stomatology, Sichuan University were analyzed retrospectively. Among them, 42 patients who received routine nursing between February 2019 and February 2020 were assigned to a control group, and 46 patients who received MDT nursing between March 2020 and February 2022 were assigned to an observation group. The two groups were compared in the changes of postoperative swallowing function and oral hygiene, postoperative swallowing-related quality of life (QoL), and the survival rate for myocutaneous flap. The risk factors affecting swallowing function were analyzed through Logistic regression. RESULTS: After one month of nursing, the score of swallowing function decreased notably in both groups, with notably lower score in the observation group than that in the control group (P < 0.05). The control group exhibited notably lower oral cleanliness than the observation group after nursing (P < 0.05). Additionally, a notably lower survival rate of myocutaneous flap was found in the control group than that in the observation group (P < 0.05). The QoL scores of the two groups increased notably after nursing, and the observation group had notably higher QoL score than the control group (P < 0.05). The extent of glossectomy and nursing plan were independent risk factors impacting the recovery of swallowing function (P < 0.05). CONCLUSION: MDT nursing have a positive impact on oral hygiene as well as the swallowing function of patients after radical resection of TC, and MDT is a protective factor for swallowing function in the patients after radical resection.

3.
J Transl Med ; 22(1): 302, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38521921

RESUMO

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.


Assuntos
Predisposição Genética para Doença , Miastenia Gravis , Humanos , Multiômica , Estudo de Associação Genômica Ampla , Miastenia Gravis/genética , Locos de Características Quantitativas/genética , Polimorfismo de Nucleotídeo Único/genética
4.
Mol Pharm ; 21(2): 661-676, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38175819

RESUMO

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.


Assuntos
Carcinoma de Células Escamosas , Ácidos Graxos Monoinsaturados , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Compostos de Amônio Quaternário , Camundongos , Animais , Micelas , RNA Interferente Pequeno/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Polietilenoglicóis , Poliésteres , Linhagem Celular Tumoral
5.
Diagn Pathol ; 18(1): 103, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37705036

RESUMO

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant tumor described in the head and neck region, especially in the gingival. We present one case arising in the gingival of right mandible, and briefly reviewed the related literature. CASE PRESENTATION: A 24-year-old male patient with a lesion of 3.5*2.0 cm in buccal gingival of right posterior mandible for 2 months. The tumor was composed of cartilaginous structures and myxoid matrix. Immunohistochemical(IHC) showed that the tumor cells to be positive for vimentin, focally positive for S-100, negative for calponin, SMA, SOX10. The Ki-67 labelling index was 80%. Fluorescent in situ Hybridization (FISH) was positive for NR4A3 rearrangement. CONCLUSIONS: Due to its unusual site and low incidence in the oral region, a combination of histological findings, immunohistochemistry, and molecular pathology as well as differential diagnosis with other diseases should be taken into consideration in the process of clinical diagnosis and treatment.


Assuntos
Condrossarcoma , Masculino , Humanos , Adulto Jovem , Adulto , Hibridização in Situ Fluorescente , Condrossarcoma/genética , Diagnóstico Diferencial , Mandíbula
6.
Int J Oral Sci ; 15(1): 23, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37286538

RESUMO

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-ß inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-ß-Zfp423-ApoD pathway.


Assuntos
Lábio , Traumatismos do Nervo Trigêmeo , Camundongos , Animais , Lábio/inervação , Estudos Prospectivos , Nervo Mandibular/cirurgia , Nervo Mandibular/patologia , Sensação/fisiologia , Traumatismos do Nervo Trigêmeo/patologia
7.
Int J Nanomedicine ; 17: 2925-2941, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814613

RESUMO

Purpose: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with more than 300,000 new cases annually. Despite advances in existing treatments, including surgery, radiation, chemotherapy, and immunotherapy, the overall survival and prognosis have remained poor. However, gene therapy based on non-viral vectors provides new ideas for the treatment of OSCC. Here, we aimed to prepare and describe the synthesis, biosafety, and preclinical efficacy of DOTAP-mPEG-PCL (DMP) in OSCC gene therapy. Methods: We prepared a nano-sized hybrid cationic micelle DMP. DMP micelles were prepared by self-assembling cationic lipid DOTAP and mPEG-PCL polymer. We evaluated the characteristics of this cationic micelle in vitro. Combined with encoding the apoptosis-inducing BimS gene, we established the DMP/phBimS complex and evaluated its anti-tumor effect in vitro. We also established a mouse tongue xenograft model to evaluate the antitumor effect of the DMP/phBimS complex in vivo through local and systemic administration prospectively. Results: The DMP cationic micelle is spherical in shape, with an average diameter of 28.32 ± 3.56 nm and an average zeta potential of 43.43 ± 0.82 mV. By activation of lipid raft-mediated endocytosis caveolin-mediated endocytosis, DMP could efficiently deliver plasmid into SCC15 cells (efficiency: 52.07% ± 1.63%), with an ideal biosecurity. When loaded by plasmid encoding the apoptosis-inducing BimS gene, the DMP/phBimS complex exhibited an obvious anti-proliferation effect of SCC15 in vitro through the apoptosis pathway (33.9% ± 2.62% apoptosis rate). By local administration, the DMP/phBimS complex showed ideal anti-tumor properties in the nude mouse tongue xenograft model, with an average tumor inhibition rate of 65.66%. Furthermore, through systematic administration, the DMP/phBimS complex obviously inhibited OSCC growth, with an average inhibition rate of 45.63% (DMP/phBimS) and an appropriate biocompatibility. Conclusion: The DMP/phBimS complex is an optional effective option for suicide gene therapy for OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Apoptose , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Cátions/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Imunoterapia , Camundongos , Micelas , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço
8.
Genesis ; 60(8-9): e23494, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35894656

RESUMO

Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.


Assuntos
Regeneração Tecidual Guiada Periodontal , Células-Tronco , Marcadores Genéticos , Ligamento Periodontal/fisiologia , Proteína GLI1 em Dedos de Zinco
9.
J Bone Miner Res ; 37(7): 1307-1320, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35443291

RESUMO

Normal development of craniofacial sutures is crucial for cranial and facial growth in all three dimensions. These sutures provide a unique niche for suture stem cells (SuSCs), which are indispensable for homeostasis, damage repair, as well as stress balance. Expansion appliances are now routinely used to treat underdevelopment of the skull and maxilla, stimulating the craniofacial sutures through distraction osteogenesis. However, various treatment challenges exist due to a lack of full understanding of the mechanism through which mechanical forces stimulate suture and bone remodeling. To address this issue, we first identified crucial steps in the cycle of suture and bone remodeling based on the established standard suture expansion model. Observed spatiotemporal morphological changes revealed that the remodeling cycle is approximately 3 to 4 weeks, with collagen restoration proceeding more rapidly. Next, we traced the fate of the Gli1+ SuSCs lineage upon application of tensile force in three dimensions. SuSCs were rapidly activated and greatly contributed to bone remodeling within 1 month. Furthermore, we confirmed the presence of Wnt activity within Gli1+ SuSCs based on the high co-expression ratio of Gli1+ cells and Axin2+ cells, which also indicated the homogeneity and heterogeneity of two cell groups. Because Wnt signaling in the sutures is highly upregulated upon tensile force loading, conditional knockout of ß-catenin largely restricted the activation of Gli1+ SuSCs and suppressed bone remodeling under physiological and expansion conditions. Thus, we concluded that Gli1+ SuSCs play essential roles in suture and bone remodeling stimulated by mechanical force and that Wnt signaling is crucial to this process. © 2022 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Suturas Cranianas , Maxila , Células-Tronco , Suturas , Proteína GLI1 em Dedos de Zinco
10.
Dev Cell ; 54(5): 639-654.e6, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32652075

RESUMO

Teeth are attached to alveolar bone by the periodontal ligament (PDL), which contains stem cells supporting tissue turnover. Here, we identified Gli1+ cells in adult mouse molar PDL as multi-potential stem cells (PDLSCs) giving rise to PDL, alveolar bone, and cementum. They support periodontium tissue turnover and injury repair. Gli1+ PDLSCs are surrounding the neurovascular bundle and more enriched in the apical region. Canonical Wnt signaling is essential for their activation. Alveolar bone osteocytes negatively regulate Gli1+ PDLSCs activity through sclerostin, a Wnt inhibitor. Blockage of sclerostin accelerates the PDLSCs lineage contribution rate in vivo. Sclerostin expression is modulated by physiological occlusal force. Removal of occlusal force upregulates sclerostin and inhibits PDLSCs activation. In summary, Gli1+ cells are the multipotential PDLSCs in vivo. Osteocytes provide negative feedback to PDLSCs and inhibit their activities through sclerostin. Physiological occlusal force indirectly regulates PDLSCs activities by fine-tuning this feedback loop.


Assuntos
Diferenciação Celular/genética , Células-Tronco Multipotentes/citologia , Osteócitos/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Animais , Células Cultivadas , Camundongos Transgênicos , Ligamento Periodontal/citologia , Periodonto/metabolismo , Regeneração/fisiologia , Células-Tronco/citologia , Via de Sinalização Wnt/genética
11.
Stem Cells Dev ; 28(19): 1310-1321, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31392933

RESUMO

Traditional two-dimensional histological sections and microcomputed tomography remain to be the major tools for studying craniofacial bones despite the complicated spatial organization of craniofacial organs. Recently, our laboratory developed the Poly(Ethylene Glycol) Associated Solvent System (PEGASOS) tissue clearing method, which can efficiently render hard tissues, including bones and teeth fully transparent without losing endogenous fluorescent signals. Complete tissue transparency enables us to acquire three-dimensional (3D) images of craniofacial bone vasculature, osteogenesis utilizing various labeling strategies, thus to investigate the spatial relationship among different tissues during postnatal craniofacial development. We found out that during the early stage of postnatal development, craniofacial osteogenesis occurs throughout the entire craniofacial bones, including the periosteum, dura, bone marrow, and suture. After 3-4 weeks, craniofacial osteogenesis is gradually restricted to the suture region and remaining bone marrow space. Similarly, craniofacial bone vasculature gradually restricts to the suture region. Osteogenesis is spatially associated with vasculature during the entire postnatal development. Importantly, we demonstrated that in adult calvarial bones, Gli1+ mesenchymal stem cells were also spatially associated with the vasculature. These findings indicate that craniofacial bones share similar osteogenesis mechanism as the long bone despite their distinct osteogenic mechanisms. In addition, the PEGASOS tissue clearing method-based 3D imaging technique is a useful new tool for craniofacial research.


Assuntos
Técnicas de Preparação Histocitológica , Imageamento Tridimensional/métodos , Osteogênese/fisiologia , Crânio/diagnóstico por imagem , Crânio/crescimento & desenvolvimento , Animais , Biomarcadores/metabolismo , Regeneração Óssea/fisiologia , Expressão Gênica , Genes Reporter , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Polietilenoglicóis/química , Crânio/anatomia & histologia , Crânio/irrigação sanguínea , Coloração e Rotulagem/métodos , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína Vermelha Fluorescente
12.
Shanghai Kou Qiang Yi Xue ; 26(2): 151-155, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28815242

RESUMO

PURPOSE: To explore the ability of nuclear factor κB (NFκB) in sustaining inflammatory cell recruitment phenotype of oral cancer associated macrophages, by using NFκB inhibitor(-Bay11-7082). METHODS: By primary culture, murine macrophages were harvested. Cal27 conditioned medium (CM) and Bay11-7082 were applied for stimulation of the macrophages. RT-PCR and ELISA were used for detecting the inflammatory cell recruitment related chemotactic factors. GraphPadPrism5 was used for statistical analysis. RESULTS: Bay11-7082 prevented the contour change into a spindle shape via Cal 27 CM. It also attenuated MCP-1, GM-CSF, MCP-5 and CCL-5 mRNA increase after Cal 27 CM stimulation (P<0.05). At protein level, impeding NFκB activation could significantly prevent MCP-1 and GM-CSF secretion from oral cancer associated macrophage (P<0.001). CONCLUSIONS: NFκB signaling may play a key role in sustaining the inflammatory cell recruitment phenotype of oral cancer associated macrophages.


Assuntos
Macrófagos , Neoplasias Bucais/metabolismo , NF-kappa B , Fenótipo , Animais , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Camundongos , Nitrilas , Transdução de Sinais , Sulfonas
13.
J Oral Maxillofac Surg ; 75(2): 403-415, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27621147

RESUMO

PURPOSE: Whether mandibular involvement by oral squamous cell carcinoma (OSCC) could be identified as a factor for cancer staging and prognosis prediction remains a subject of debate. In addition, the influence of different types of mandibular invasion (cortical or medullary invasion) on patients' prognosis remains unclear. The aim of this systematic review was to establish whether mandibular invasion or its subset should be considered an independent prognostic factor for patients with OSCC. MATERIALS AND METHODS: The search for eligible studies was performed according to the predesigned inclusion criteria for a systematic review. Mandibular invasion and invasion depth were considered the primary and secondary predictor variables, respectively. The electronic search was performed using 12 databases. Manual searching covered 14 related journals and references of the included studies were scanned. The risk of bias assessment was evaluated by 2 reviewers using risk-of-bias assessment tools recommended by Saltaji et al (Angle Orthod 82:1115, 2012). Two reviewers extracted the data in duplicate. RevMan 5.2 was used for meta-analysis to assess the primary outcomes (disease-free survival and overall survival) and the secondary outcomes (2- and 5-year survival rate and local control). RESULTS: Eighteen studies (total, 3,756 participants) were included and used as the study sample. Among these included studies, 7 had an unclear risk of bias and the remaining showed a high risk. The results of the meta-analyses showed a significant relation between mandibular invasion and overall survival (P = .04) and, most importantly, that medullary involvement (P = .0001), but not cortical involvement (P = .66), could decrease overall survival. When focusing on disease-specific survival, mandibular medullary involvement predicted a poor disease-specific survival (P < .0001), but cortical involvement showed no effect (P = .66). CONCLUSION: This review showed that OSCC mandibular medullary invasion, and not mandibular invasion or mandibular cortical invasion, could be an independent prognostic factor for patients.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Mandibulares/secundário , Neoplasias Bucais/diagnóstico , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Bucais/patologia , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Prognóstico
14.
Endocrinology ; 158(2): 402-409, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27813675

RESUMO

The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. Tight control of steroid production is essential for multiple processes involved in reproduction, including follicular development, ovulation, and endometrial synchronization. Recently, there has been a growing interest in the role of noncoding RNAs in the regulation of reproduction. Here we demonstrate that StAR is a novel target of the microRNA let-7, which itself is regulated by the long noncoding RNA (lncRNA) H19. Using human and murine cell lines, we show that overexpression of H19 stimulates StAR expression by antagonizing let-7, which inhibits StAR at the post-transcriptional level. Our results uncover a novel mechanism underlying the regulation of StAR expression and represent the first example of lncRNA-mediated control of the rate-limiting step of steroidogenesis. This work thus adds to the body of literature describing the multiple roles in oncogenesis, cellular growth, glucose metabolism, and now regulation of steroidogenesis, of this complex lncRNA.


Assuntos
MicroRNAs/metabolismo , Fosfoproteínas/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular , Humanos , Camundongos
15.
Nat Commun ; 6: 10221, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26687445

RESUMO

DNA methylation is essential for mammalian development and physiology. Here we report that the developmentally regulated H19 lncRNA binds to and inhibits S-adenosylhomocysteine hydrolase (SAHH), the only mammalian enzyme capable of hydrolysing S-adenosylhomocysteine (SAH). SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases that methylate diverse cellular components, including DNA, RNA, proteins, lipids and neurotransmitters. We show that H19 knockdown activates SAHH, leading to increased DNMT3B-mediated methylation of an lncRNA-encoding gene Nctc1 within the Igf2-H19-Nctc1 locus. Genome-wide methylation profiling reveals methylation changes at numerous gene loci consistent with SAHH modulation by H19. Our results uncover an unanticipated regulatory circuit involving broad epigenetic alterations by a single abundantly expressed lncRNA that may underlie gene methylation dynamics of development and diseases and suggest that this mode of regulation may extend to other cellular components.


Assuntos
Adenosil-Homocisteinase/metabolismo , RNA Longo não Codificante/metabolismo , Adenosil-Homocisteinase/genética , Animais , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Genoma , Humanos , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Camundongos , Ligação Proteica , RNA Longo não Codificante/genética , S-Adenosil-Homocisteína/metabolismo , DNA Metiltransferase 3B
16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(4): 887-91, 904, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26710464

RESUMO

To realize the accurate positioning and quantitative volume measurement of tumor in head and neck tumor CT images, we proposed a level set method based on augmented gradient. With the introduction of gradient information in the edge indicator function, our proposed level set model is adaptive to different intensity variation, and achieves accurate tumor segmentation. The segmentation result has been used to calculate tumor volume. In large volume tumor segmentation, the proposed level set method can reduce manual intervention and enhance the segmentation accuracy. Tumor volume calculation results are close to the gold standard. From the experiment results, the augmented gradient based level set method has achieved accurate head and neck tumor segmentation. It can provide useful information to computer aided diagnosis.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Tomografia Computadorizada por Raios X , Diagnóstico por Computador , Humanos , Carga Tumoral
17.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 33(3): 326-8, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26281267

RESUMO

Anterolateral thigh flap is perfect for reconstructing maxillofacial soft tissue defects. This tissue has been widely used by clinicians, but often causes operation difficulties because of vascular variation. In this paper, we report a case where anteromedial thigh was used as new donor site when the vascular anatomic variation of anterolateral thigh perforator flap induced a failure in the flap harvest. Moreover, this paper discusses the anatomy and application of anteromedial thigh flap.


Assuntos
Anormalidades Maxilofaciais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Coxa da Perna/cirurgia , Humanos , Retalho Perfurante
18.
J Oral Maxillofac Surg ; 73(9): 1875.e1-11, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26022068

RESUMO

PURPOSE: To detect the diagnostic efficacy of emission computed tomography (ECT) in detecting mandibular invasion caused by head and neck cancers. MATERIALS AND METHODS: Thirteen databases were searched electronically to retrieve studies for inclusion and a manual search also was conducted. Study inclusion, data extraction, and quality assessment were completed by 2 reviewers independently. Meta-DiSc 1.4 and STATA 11.0 were used to conduct the meta-analysis. RESULTS: Seventeen studies involving 668 participants were included. One study had a low risk of bias, 2 had a high risk, and the rest had unclear risk. Meta-analysis showed that for the diagnosis of mandibular invasion single-photon ECT (SPECT) had a mean sensitivity (SEN) of 0.96, a mean specificity (SPE) of 0.66, an area under the curve (AUC) of 0.8989, and a Q* (point on the summary reviewer operator characteristic curve when SEN equaled SPE) of 0.8300. Positron emission tomography combined with computed tomography (PET/CT) had a mean SEN of 0.83, a mean SPE of 0.90, an AUC of 0.9290, and a Q* of 0.8640. The comparison between the diagnostic efficacy of SPECT and PET/CT showed that SPECT was superior for SEN (P = .0014) and PET/CT had a significantly better SPE (P = .001). The summary diagnostic efficacy between these modalities did not differ significantly (P > .05). CONCLUSIONS: The present clinical evidence showed that SPECT is an excellent tool to exclude patients with no mandibular invasion, but is not as good as PET/CT to confirm the diagnosis.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Mandibulares/secundário , Invasividade Neoplásica , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Neoplasias Mandibulares/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
20.
PLoS One ; 9(11): e112267, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25397614

RESUMO

BACKGROUND: Diagnosis of mandibular involvement caused by head and neck cancers is critical for treatment. We performed a meta-analysis to determine the diagnostic efficacy of MR for distinguishing mandibular involvement caused by head and neck cancers. METHODS: Thirteen databases were searched electronically and hand-searching was also done. Two reviewers conducted study inclusion, data extractions, and quality assessment of the studies independently. Meta-disc 1.4 and STATA 11.0 were used to conduct the meta-analysis. RESULTS: 16 studies involving a total of 490 participants underwent MR examinations and were accounted for in this meta-analysis. Among the included studies, 2 had high risk of bias, while the rest had unclear risk of bias. Meta-regression showed that the slight clinical and methodological heterogeneities did not influence the outcome (P>0.05). Meta-analysis indicated that the MR for the diagnosis of mandibular involvement had a pooled sensitivity (SEN) of 78%, specificity (SPE) of 83%, positive likelihood ratio (+LR) of 3.80, negative likelihood ratio (-LR) of 0.28, diagnostic odds ratio (DOR) of 28.94, area under curve (AUC) of 0.9110, and Q* of 0.8432. Two studies detected the diagnostic efficacy of MR for the mandibular medullar invasion, and only one study reported the inferior alveolar canal invasion, which made it impossible to include it in our meta-analysis. In comparing to CT, MR had a higher SEN without statistical significance (P = 0.08), but a significantly lower SPE (P = 0.04). The synthesized diagnostic efficacy (AUC and Q*) on mandibular involvement was similar between the two modalities (P>0.05). CONCLUSIONS: Present clinical evidence showed that MR had an acceptable diagnostic value in detecting mandibular involvement caused by head and neck cancers. MR exceeded CT in diagnosing patients with mandibular invasion (higher sensitivity than CT) but was less efficacious to exclude patients without the mandibular invasion (lower specificity than CT).


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Imageamento por Ressonância Magnética , Mandíbula/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Neoplasias Bucais/diagnóstico , Viés de Publicação , Curva ROC , Análise de Regressão , Tomografia Computadorizada por Raios X
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