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1.
Sci Rep ; 14(1): 4402, 2024 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388665

RESUMEN

The DNA repair gene PARP1 and NF-κB signalling pathway affect the metastasis of breast cancer by influencing the drug resistance of cancer cells. Therefore, this study focused on the value of the DNA repair gene PARP1 and NF-κB pathway proteins in predicting the postoperative metastasis of breast cancer. A nested case‒control study was performed. Immunohistochemical methods were used to detect the expression of these genes in patients. ROC curves were used to analyse the predictive effect of these factors on distant metastasis. The COX model was used to evaluate the effects of PARP1 and TNF-α on distant metastasis. The results showed that the expression levels of PARP1, IKKß, p50, p65 and TNF-α were significantly increased in the metastasis group (P < 0.001). PARP1 was correlated with IKKß, p50, p65 and TNF-α proteins (P < 0.001). There was a correlation between IKKß, p50, p65 and TNF-α proteins (P < 0.001). ROC curve analysis showed that immunohistochemical scores for PARP1 of > 6, IKKß of > 4, p65 of > 4, p50 of > 2, and TNF-α of > 4 had value in predicting distant metastasis (SePARP1 = 78.35%, SpPARP1 = 79.38%, AUCPARP1 = 0.843; Sep50 = 64.95%, Spp50 = 70.10%, AUCp50 = 0.709; SeTNF-α = 60.82%, SpTNF-α = 69.07%, AUCTNF-α = 0.6884). Cox regression analysis showed that high expression levels of PARP1 and TNF-α were a risk factor for distant metastasis after breast cancer surgery (RRPARP1 = 4.092, 95% CI 2.475-6.766, P < 0.001; RRTNF-α = 1.825, 95% CI 1.189-2.799, P = 0.006). Taken together, PARP1 > 6, p50 > 2, and TNF-α > 4 have a certain value in predicting breast cancer metastasis, and the predictive value is better when they are combined for diagnosis (Secombine = 97.94%, Spcombine = 71.13%).


Asunto(s)
Neoplasias de la Mama , FN-kappa B , Humanos , Femenino , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Quinasa I-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Estudios de Casos y Controles , Factor de Transcripción ReIA/metabolismo , Reparación del ADN/genética , Poli(ADP-Ribosa) Polimerasa-1/genética , Poli(ADP-Ribosa) Polimerasa-1/metabolismo
2.
Sci Rep ; 13(1): 22922, 2023 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-38129538

RESUMEN

Breast cancer (BC) is a severe danger to women's lives and health globally. S100A11 is aberrantly expressed in many carcinomas and serves a crucial function in cancer development. However, the role of S100A11 in BC is unclear. In this study, we utilized multiple databases and online tools, including the TCGA database, cBioPortal, and STRING, to evaluate the significance of S100A11 in BC prognosis and immune infiltration. We found that S100A11 was considerably more abundant in BC tissues. Survival analysis indicated that individuals with S100A11 high expression of BC had shorter overall survival. Multivariate Cox regression analysis revealed that high S100A11 expression independently influenced the poor outcome of patients with BC (HR = 1.738, 95%CI 1.197-2.524). Our nomogram incorporating five factors, including S100A11, age, clinical stage, N, and M, was developed to anticipate the survival probability in BC prognosis. The model demonstrated good consistency and accuracy. Furthermore, the mutation rete of S100A11 was 14%. Survival analysis suggested that breast cancer patients with S100A11 mutation had a worse prognosis. KEGG pathway enrichment analysis revealed that S100A11 may be mainly involved in the IL-17 signaling pathway. Finally, we discovered a correlation between S100A11 expression and immune cell infiltration on BC. S100A11 expression was positively associated with 17 immune checkpoint-related genes. In conclusion, this study indicates that S100A11 may contribute to a worse prognosis for BC and potentially has a significant impact through its influence on immune cell infiltration and the IL-17 signaling pathway.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Humanos , Femenino , Neoplasias de la Mama/genética , Pronóstico , Interleucina-17 , Nomogramas , Proteínas S100/genética
3.
Technol Cancer Res Treat ; 22: 15330338231164887, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36959742

RESUMEN

Aim: This study aimed to investigate the role of MARCH2 (membrane-associated RING-CH2) in the progression, invasion, and migration of colorectal cancer (CRC). Methods: In this study, the expression levels of MARCH2 and E-cadherin in CRC tissues were detected by immunohistochemistry through retrospective study, and their correlation was analyzed. After silencing the MARCH2 gene using SiRNA MARCH2-1/-2, the invasion and migration abilities of SW480 cells were detected using Transwell and Scratch assay, respectively. Quantitative real-time PCR (qRT-PCR) and Western blotting assays were performed to detect the expression levels of epithelial-mesenchymal transition (EMT) related markers. Results: As compared to adjacent tissues, the MARCH2 expression level was significantly overexpressed in the CRC tissues, and correlated with tumor size, pathological grade, lymph node metastasis, and survival time. MARCH2 was negatively correlated with E-cadherin. MARCH2 silencing significantly restrained the invasion and migration abilities of SW480 cells in vitro. Meanwhile, the MARCH2 silencing also upregulated the mRNA and protein expression levels of E-cadherin and downregulated those of Vimentin. Conclusions: The high expression of MARCH2 was unfavorable for patients' survival. Thus, MARCH2 might be an independent predictor for CRC patients, affecting the invasion and metastasis of CRC through EMT.


Asunto(s)
Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Humanos , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Estudios Retrospectivos , Neoplasias Colorrectales/patología , Proliferación Celular/genética , Cadherinas/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica
4.
Virchows Arch ; 481(6): 847-852, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36301367

RESUMEN

Metastasis is the main cause of colorectal cancer (CRC)-related death and lymph node plays a vital role in this process. Long noncoding RNAs (lncRNAs) are emerging as an important factor of biological progress in cancers. However, lncRNAs related to CRC metastasis was rarely reported.CLAN expression data of tumor tissues and normal tissues were obtained from GEPIA database and 23 paired tumor and normal samples of patients. CLAN expression of 85 patients was carried out with RNA extracted from FFPE samples and quantified with qRT-PCR. Patients' clinical features were collected from department of Pathology of the Affiliated Hospital of Southwest Medical University. Immunohistochemistry staining was used to detect the metastasis-related proteins.CLAN was highly expressed in tumor tissues. And the expression level was not correlated with age, gender, differentiation, and location of CRC patients. Also, CLAN expression did not correlated with budding, LVI, and TILs. However, CLAN expression was strongly associated with lymph node metastasis and higher TNM stage. CLAN changed the lymphatic vessel density by promoting lymphangiogenesis but CLAN did not affect the blood vessel density.CLAN was a unique lncRNA that promoted lymphangiogenesis to accelerate CRC metastasis. CLAN might play a unique role in tumor early dissemination through lymphatic vessel.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD , Proteínas de Unión al Calcio , Neoplasias Colorrectales , ARN Largo no Codificante , Humanos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Linfangiogénesis , Metástasis Linfática , ARN Largo no Codificante/metabolismo , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas de Unión al Calcio/genética
5.
J Environ Public Health ; 2022: 5749359, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35942148

RESUMEN

From the cassette era to the CD era to the digital music era, the quantity of music has grown rapidly. People cannot easily search for the desired music without classifying enormous music resources and developing a successful music retrieval system. By examining users' historical listening patterns for personalised recommendations, the music recommendation algorithm can lessen message fatigue for users and enhance user experience. Relying on manual labelling is how traditional music is classified. It would be inefficient and unrealistic to attempt to classify music using manual labelling in the age of big data. Feature extraction and neural networks are the tools employed in this paper. The model's parameters can be trained using conventional gradient descent techniques, and the model's trained convolution neural network can learn the image's features and finish the extraction and classification of the features. This algorithm is 12 percent superior to the conventional algorithm, according to the research in this paper. It has strong ability and is appropriate for widespread implementation with the same number of iterations.


Asunto(s)
Música , Algoritmos , Macrodatos , Humanos , Redes Neurales de la Computación
6.
J Dermatol Sci ; 106(1): 37-44, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35346558

RESUMEN

BACKGROUND: Loricrin keratoderma is a rare early-onset autosomal dominant skin disorder. At present, no clinical reports have been published on characteristics of progressive aggravation and late-onset. OBJECTIVES: To identified a new-found pedigree with c.323 G>C mutation leading to progressive aggravation and late-onset loricrin keratoderma. METHODS: Targeted next-generation sequencing of 267 genes associated with all skin abnormalities, sanger sequencing, and bioinformatics tools were used to identify the mutation in this new-found pedigree. Palm skin biopsy was used to observe the clinicopathological features of patient. Further, we constructed pcDNA3.1/V5-His-wild-LORICRIN, pcDNA3.1/V5-His-c.323G>C-LORICRIN, and pcDNA3.1/V5-His-730insG-LORICRIN vectors, nucleofected into HaCaT strain to observe the subcellular localization of loricrin by using the laser scanning confocal microscopy. RESULTS: The proband and his affected father carried a heterozygous c.323 G>C missense mutation (p.Gly108Ala) on LORICRIN. Bioinformatics analysis hinted that it had potential pathogenicity; the types of ligands, enzyme commission active sites, and the spatial structure of protein changed enormously. Laser scanning confocal microscopy showed that the signals from cells transfected with the pcDNA3.1/V5-His-730insG-LORICRIN vector were distributed mainly in the nucleus, whereas those from cells transfected with the pcDNA3.1/V5-His-c.323G>C-LORICRIN vector were mainly located in the cytoplasm. Wild type loricrin was distributed in the nucleus and cytoplasm homogeneously CONCLUSION: The heterozygous c.323G>C missense mutation on LORICRIN caused late-onset and progressive loricrin keratoderma in this large Chinese family. Our study revealed that a large number of loricrin gathered in the cytoplasm may disturb the normal proliferation and terminal differentiation of keratinocytes and lead to the late-onset loricrin keratoderma disease.


Asunto(s)
Proteínas de la Membrana , Mutación Missense , Humanos , China , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Linaje , Enfermedades Cutáneas Genéticas
7.
J Oral Pathol Med ; 51(2): 134-145, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34689367

RESUMEN

OBJECTIVES: This study aimed to determine expressions of methyltransferase-like 3 (METTL3) and METTL14, two enzymes essential for mRNA methylation at the adenosine (m6 A), in oral squamous cell carcinoma (OSCC) and to investigate in vitro aggressiveness of their aberrant expressions. METHODS: METTL3 and METTL14 expressions in 50 OSCC and 11 normal oral tissues were examined by immunohistochemistry. METTL3 and METTL14 expressions and m6 A amounts were determined in three OSCC cell lines, including HN5, HN6, and HN15. Cell proliferation, migration, and invasion were studied by BrdU, wound healing, and Transwell chamber assays, after silencing of METTL3, METTL14, or both by siRNA transfection. RESULTS: Immunostaining of METTL3 and METTL14 was localized in cancer cell nuclei. The mean percentages of METTL3- and METTL14-positive cells were significantly increased in OSCC tissues (p < 0.001). The percentages of METTL3- and METTL14-positive cells were correlated with the advanced pTNM stages (p < 0.05) and with the degrees of histopathological differentiation in OSCC (r = 0.564 and r = 0.316, respectively; p < 0.001). By the COX multivariate analysis, both overexpressed METTL3 and METTL14 were significantly associated with short overall survival (p < 0.05). Both METTL3 and METTL14 expressions and the m6 A amounts were significantly increased in HN6 (p < 0.05). Silencing of METTL3 and METTL14 in HN6 significantly inhibited cell proliferation (p < 0.01), but it failed to mitigate cell migration or invasion. CONCLUSIONS: METTL3 and METTL14 are overexpressed in OSCC tissues and in the HN6 OSCC cell line that promotes cell proliferation. Overexpressed METTL3 or METTL14 is found to be an independent prognostic factor for short overall survival in patients with OSCC.


Asunto(s)
Metiltransferasas/metabolismo , Neoplasias de la Boca/enzimología , Carcinoma de Células Escamosas de Cabeza y Cuello/enzimología , Línea Celular Tumoral , Proliferación Celular , Humanos , Metiltransferasas/genética , ARN Mensajero
8.
J Mol Histol ; 52(6): 1129-1144, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34727293

RESUMEN

Glaucoma filtration surgery (GFS) is a classic operation for the treatment of glaucoma, which is the second leading cause of blindness, and scar formation caused by excessive human Tenon's capsule fibroblasts (HTFs) activation is responsible for surgery failure. However, the mechanism underlying excessive HTFs activation is largely unknown. Studies have revealed that N6-methyladenosine (m6A), which is one of the most common posttranscriptional modifications, plays an important role in multiple types of cellular processes. First, we isolated and identified primary HTFs and found that transforming growth factor-ß1 (TGF-ß1) enhanced cell viability and promoted cell proliferation and extracellular matrix (ECM) deposition in HTFs. We subsequently found that TGF-ß1 elevated the quantity of m6A and promoted the expression of m6A "writers", in the process from DNA to RNA, adenylate was methylated at the sixth N position by methylases methyltransferase-like 3 (METTL3). Furthermore, we demonstrated that METTL3 repression inhibited the promotion of cell viability, proliferation and ECM deposition in HTFs treated with TGF-ß1. We then illustrated that increased METTL3 played a role by promoting Smad3 in TGF-ß1-induced HTFs. We subsequently demonstrated that the METTL3/Smad3 regulatory axis was aberrantly expressed in the rabbit model of GFS. Thus, our study reveals that METTL3 indeed plays a role in modulating Smad3 in TGF-ß1-induced HTFs and further provides novel theoretical strategies based on METTL3 for the inhibition of scar formation after GFS.


Asunto(s)
Fibroblastos/metabolismo , Regulación de la Expresión Génica , Metiltransferasas/genética , Transducción de Señal , Proteína smad3/metabolismo , Cápsula de Tenon/citología , Factor de Crecimiento Transformador beta/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animales , Biomarcadores , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Matriz Extracelular/metabolismo , Glaucoma/genética , Glaucoma/metabolismo , Glaucoma/cirugía , Humanos , Inmunohistoquímica , Metiltransferasas/metabolismo , Conejos , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo
9.
Sci Rep ; 10(1): 19626, 2020 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-33184404

RESUMEN

Breast cancer is the most common malignant tumor in China and even in the world. DNA repair genes can lead to tumor metastasis by affecting cancer cell resistance. Studies have preliminarily shown that DNA repair genes are related to breast cancer metastasis, but it is not clear whether they can be used as a prediction of the risk of breast cancer metastasis. Therefore, this study mainly discusses the predictive value of DNA repair genes in postoperative metastasis of breast cancer. The nested case-control method was used in patients with breast cancer metastasis after surgery (n = 103) and patients without metastasis after surgery (n = 103). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. In protein expression, PARP1 (OR 1.147, 95% CI 1.067 ~ 1.233, P < 0.05), XRCC4 (OR 1.088, 95% CI 1.015 ~ 1.166, P < 0.05), XRCC1 (OR 1.114, 95% CI 1.021 ~ 1.215, P < 0.05), ERCC1 (OR 1.068, 95% CI 1.000 ~ 1.141, P < 0.10) were risk factors for postoperative metastasis of breast cancer. In addition, we used the ROC curve to study the optimal critical values of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA combined with the Youden index, and the effects of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA on breast cancer metastasis were verified again. Among them, the risk of metastasis in the PARP1 high expression group was 3.286 times that of the low expression group (OR 3.286, 95% CI 2.013 ~ 5.364, P < 0.05). The risk of metastasis in the XRCC4 high expression group was 1.779 times that of the low expression group (OR 1.779, 95% CI 1.071 ~ 2.954, P < 0.05). The risk of metastasis in patients with ERCC1 high expression group was 2.012 times that of the low expression group (OR 2.012, 95% CI 1.056 ~ 3.836, P < 0.05). So we can conclude that protein expression of PARP1 (cut-off value = 6, Se = 76.70%, Sp = 79.61%), XRCC4 (cut-off value = 6, Se = 78.64%0, Se = 79.61%), ERCC1 (cut-off value = 3, Se = 89.32%, Sp = 50.49%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of metastasis will increases. Due to PARP1, XRCC4 and ERCC1 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-XRCC4 = 0.343; rPAPR1-ERCC1 = 0.335; rXRCC4-ERCC1 = 0.388). The combined diagnosis of the PARR1, XRCC4 and ERCC1 have greater predictive value for the risk of metastasis of breast cancer (Se = 94.17%, Sp = 75.73%; OR 11.739, 95% CI 2.858 ~ 40.220, P < 0.05). The postoperative metastasis of breast cancer could be effectively predicted when the immunohistochemical scores met PARP1 (IHC score) > 6, XRCC4 (IHC score) > 6 and ERCC1 (IHC score) > 3. In addition, the combined diagnosis of PARP1, XRCC4 and ERCC1 has great predictive value for the risk of breast cancer metastasis.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Endonucleasas/genética , Endonucleasas/metabolismo , Expresión Génica , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/genética , Poli(ADP-Ribosa) Polimerasa-1/genética , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Reacción en Cadena de la Polimerasa , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Riesgo
10.
Exp Cell Res ; 387(2): 111802, 2020 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-31877306

RESUMEN

Glaucoma filtration surgery (GFS) is a classic surgical method used to treat glaucoma, the second leading cause of blindness. Scar formation caused by excessive Tenon's capsule fibroblast activation leads to surgical failure. However, the mechanism underlying this activation is largely unknown. In this study, we first isolated primary human Tenon's capsule fibroblasts (HTFs) and found that TGF-ß promoted the viability, proliferation and extracellular matrix (ECM) deposition of HTFs. Then, we showed that TGF-ß promoted the expression of H19 in HTFs and that suppression of H19 inhibited the effect of TGF-ß on HTFs. Furthermore, we revealed that H19 exerted its effects by interacting with miR-200a in TGF-ß-treated HTFs. Additionally, we showed that ß-catenin was a target of miR-200a in TGF-ß-treated HTFs. We also demonstrated that H19 acted by modulating the H19/miR-200a/ß-catenin regulatory axis in TGF-ß-treated HTFs. Ultimately, we found that the components of the H19/miR-200a/ß-catenin regulatory axis were aberrantly expressed in a rat model of GFS. Our results show that H19 indeed acts by modulating ß-catenin expression via miR-200a in TGF-ß-treated HTFs, thus providing a novel rationale for the development of H19-based strategies to attenuate scar formation after GFS.


Asunto(s)
Proliferación Celular/genética , Matriz Extracelular/genética , Fibroblastos/fisiología , ARN Largo no Codificante/genética , Cápsula de Tenon/fisiología , Factor de Crecimiento Transformador beta1/genética , Animales , Cicatriz/genética , Fibrosis/genética , Regulación de la Expresión Génica/genética , Glaucoma/genética , Masculino , MicroARNs/genética , Ratas , Ratas Sprague-Dawley , beta Catenina/genética
11.
Acta Biochim Biophys Sin (Shanghai) ; 51(4): 411-421, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30811524

RESUMEN

To investigate the neuroprotective effects of the mitochondria-targeted antioxidant Szeto-Schiller peptide 31 (SS-31) in a rat experimental glaucoma model, SS-31 was intraperitoneally (IP) injected into Sprague-Dawley rats, followed by intracameral injection of polystyrene microspheres to induce elevated intraocular pressure (IOP). After 6 weeks, electroretinography (ERG) and flash visual-evoked potentials (F-VEPs) were recorded to assess retinal function. Hematoxylin-eosin staining was performed on retinal cross-sections to measure ganglion cell complex (GCC) thickness. Apoptotic retinal cells were assessed by TUNEL staining. Brn3a-positive retinal ganglion cells (RGCs) were counted in retinal flat mounts via immunofluorescence. The retinal total SOD, SOD2, and MDA expression levels were assessed in retinal tissue homogenates. The cyt c, Bax, and Bcl-2 protein levels in rat retinas were detected by western blot analysis. Bax and Bcl-2 expressions were also evaluated using immunohistochemistry in paraffinized sections. Our results showed that the rats that received microsphere injection developed elevated IOP. SS-31 ameliorated the reductions in the a- and b-wave amplitudes on ERG and the F-VEP amplitude in glaucomatous eyes. GCC thickness was preserved, TUNEL-positive cells were decreased in the retina, and Brn3a-positive RGCs were increased in the SS-31-treated glaucoma group compared with those in the non-treated glaucoma group. SS-31 significantly reduced MDA levels and increased SOD2 levels after glaucoma induction. Significant suppression of cyt c release, upregulation of Bcl-2, and downregulation of Bax were observed following SS-31 administration. In summary, SS-31 exerts neuroprotective effects in this experimental glaucoma model by inhibiting mitochondrial dysfunction and therefore represents a promising therapeutic agent for glaucoma.


Asunto(s)
Antioxidantes/farmacología , Glaucoma/prevención & control , Mitocondrias/efectos de los fármacos , Oligopéptidos/farmacología , Animales , Antioxidantes/administración & dosificación , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Electrorretinografía , Glaucoma/metabolismo , Glaucoma/fisiopatología , Inyecciones Intraperitoneales , Presión Intraocular/efectos de los fármacos , Masculino , Mitocondrias/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Oligopéptidos/administración & dosificación , Ratas Sprague-Dawley , Retina/efectos de los fármacos , Retina/metabolismo , Retina/fisiopatología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/fisiología
12.
Virol J ; 15(1): 94, 2018 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-29801461

RESUMEN

BACKGROUND: Currently, the role of human papillomavirus (HPV)-58 in southwestern China has been unexplored. Although there is some controversy, it is proposed that the viral load of HPV correlates with the severity of intraepithelial lesions. METHODS: We identified 7747 patients from south Sichuan and adjacent regions who were diagnosed with HPV between 2013 and 2017. The HR-HPV subtype distribution was analyzed and the patient's viral loads were quantified using real-time RT-PCR. RESULTS: Among all 7747 patients screened for HPV genotypes, 1728 patients (22.31%) were identified as having HR-HPV subtypes. In patients without intraepithelial lesions (12.41%), HPV-52, HPV-16, and HPV-58 were the three most prevalent HR-HPV subtypes. Moreover, HPV-16, HPV-58, and HPV-33 were the most prevalent subtypes in patients with cervical intraepithelial neoplasia grade II (CINII) (42.86%) and grade III (CINIII) (59.81%), and accounted for the majority of invasive cervical cancer (ICC) (69.34%). Thus, viral loads of HPV-58, HPV-16, and HPV-33 positively correlated with the severity of cervical lesions (P < 0.001, P = 0.016, P = 0.026, respectively). Using receiver operating characteristic (ROC) curve analysis, the optimum thresholds for predicting severe intraepithelial lesions of cases (CINI, CINIII and ICC) with HPV-16, HPV-58, and HPV-33, respectively, were obtained, which were 1, 0.93, and 0.25, respectively. CONCLUSION: In our study, we showed that HPV-16 was the most common carcinogenic HPV subtype in southwestern China followed by HPV-58 and HPV-33. Viral loads of these subtypes are associated with the severity of premalignant lesions in the cervix.


Asunto(s)
Alphapapillomavirus/genética , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/patología , Lesiones Precancerosas/patología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alphapapillomavirus/clasificación , Alphapapillomavirus/aislamiento & purificación , Alphapapillomavirus/patogenicidad , Cuello del Útero/metabolismo , Cuello del Útero/patología , China/epidemiología , Femenino , Genotipo , Papillomavirus Humano 16/clasificación , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Riesgo , Índice de Severidad de la Enfermedad , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Carga Viral , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología
13.
J Mater Sci Mater Med ; 26(8): 225, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26286760

RESUMEN

PEG-PCL-PEG (PECE) hydrogel for intracameral injection as a sustained delivery system can get a stable release of the medication and achieve an effective local concentration. The injectable PECE hydrogel is thermosensitive nano-material which is flowing sol at low temperature and can shift to nonflowing gel at body temperature. This study evaluated the intracameral injection of bevacizumab combined with a PECE hydrogel drug release system on postoperative scarring and bleb survival after experimental glaucoma filtration surgery. The best result was achieved in the bevacizumab loaded PECE hydrogels group, which presented the lowest IOP values after surgery. And the blebs were significantly more persistent in this group. Histology, Massion trichrome staining and immunohistochemistry further demonstrated that glaucoma filtration surgery in combination with bevacizumab loaded PECE hydrogel resulted in good bleb survival due to scar formation inhibition. In conclusions, this study demonstrated that bevacizumab-loaded PECE hydrogel for intracameral injection as a sustained delivery system provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Sistemas de Liberación de Medicamentos , Cirugía Filtrante , Glaucoma/tratamiento farmacológico , Glaucoma/cirugía , Presión Intraocular/efectos de los fármacos , Poliésteres , Polietilenglicoles , Actinas/metabolismo , Animales , Cicatriz/prevención & control , Modelos Animales de Enfermedad , Cirugía Filtrante/efectos adversos , Glaucoma/fisiopatología , Hidrogeles , Complicaciones Posoperatorias/prevención & control , Conejos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
14.
Med Oncol ; 31(11): 245, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25304007

RESUMEN

XRCC2 is an essential part of the homologous recombination repair pathway. However, relatively little is known about the effect of XRCC2 gene C41657T and G4234C polymorphisms on the individual susceptibility to colorectal cancer (CRC). The purpose of this study was to investigate the association between XRCC2 gene C41657T and G4234C polymorphisms and CRC and to explore the relationship among the polymorphisms and clinicopathologic parameters and protein expression levels of XRCC2. A hospital-based case-control study was conducted with 246 CRC cases and 262 healthy controls. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. XRCC2 protein was analyzed by immunohistochemistry for the paraffin sections of 120 CRC cases. The study data showed that the C41657T genotypes were associated with the risk of CRC. The CT/TT genotypes and T allele were overrepresented among the CRC cases. Compared with CC, CT/TT enhanced the risk of CRC (odds ratio = 1.646, 95 % confidence interval = 1.127-2.404, P = 0.010). XRCC2 protein expression of CRC patients with CT/TT genotypes was significantly higher than that of the patients with CC genotype (χ (2) = 4.887, P = 0.027). XRCC2 gene G4234C polymorphisms have no relevance to the risk of CRC. Our findings suggest that XRCC2 C41657T polymorphism may adjust the XRCC2 expression and might influence susceptibility of CRC.


Asunto(s)
Pueblo Asiatico/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Artículo en Inglés | MEDLINE | ID: mdl-24804274

RESUMEN

Currently, filtration surgery has been considered as the most effective therapy for glaucoma; however, the scar formation in the surgical area may often lead to failure to the procedure. An implanted drug delivery system may provide localized and sustained release of a drug over an extended period. Poly (ethylene glycol)-poly (ε-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been successfully synthesized and determined as thermosensitive and biocompatible. In order to overcome the limitations of common local ophthalmic medications, we investigated the function of a self-assembled PECE hydrogel as an intracameral injection-implanted drug carrier to inhibit the formation of postoperative scarring. Following bevacizumal-loaded hydrogel intracameral injection into rabbit eyes, the status of the bleb and filtration fistula formed following the filtering surgery were examined through pathologic evaluation. Due to the sustained release of bevacizumab from the hydrogel, neovascularization and scar formation were inhibited; moreover, there were no corneal abnormalities and other ocular tissue damage found in the rabbits. This suggests that the PECE hydrogel may be considered as the novel biomaterial with potential as a sustained release system in glaucoma filtering surgery. Further studies require in shedding the light on the subject.

16.
DNA Cell Biol ; 32(5): 236-42, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23581553

RESUMEN

To investigate the association of survivin -31G/C, -141G/C, and -241T/C polymorphisms with colorectal cancer (CRC) susceptibility and explore the mechanisms of the survivin polymorphism in CRC development. A case-control study was conducted of 275 CRC cases and 270 healthy controls. Polymorphisms of survivin -31G/C, -141G/C, and -241T/C were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Survivin and Ki-67 expression was analyzed by immunohistochemistry by the Envision technique for the paraffin sections of 152 CRC. It showed that the -31G/C genotype and allele distribution were significantly different between the CRC cases and controls. The -31CC genotype and -31C allele were over-represented among the CRC cases. Compared with the CC genotype, the GC and GG genotypes had a significantly decreased risk of CRC (p=0.015). Survivin and Ki-67 expression of patients with the CC genotype was significantly higher than the patients with the GC and GG genotypes. In addition, a significantly positive correlation was found between expression of Survivin and Ki-67. There were no significant difference of the -141G/C and -241T/C polymorphism distributions among cases and controls. Survivin 31G/C may adjust the Survivin expression, and it might contribute to a risk of developing CRC.


Asunto(s)
Carcinoma/genética , Neoplasias Colorrectales/genética , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Pueblo Asiatico/estadística & datos numéricos , Carcinoma/epidemiología , Carcinoma/etnología , Carcinoma/metabolismo , Estudios de Casos y Controles , China/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción/fisiología , Polimorfismo de Nucleótido Simple/fisiología , Población , Survivin
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