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1.
Int J Cancer ; 153(6): 1172-1181, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37260277

RESUMEN

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.


Asunto(s)
COVID-19 , Neoplasias del Cuello Uterino , Femenino , Humanos , COVID-19/epidemiología , Pandemias , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/terapia , China/epidemiología , Hospitales Universitarios
2.
J Am Acad Dermatol ; 89(4): 711-718, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37356626

RESUMEN

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use. OBJECTIVE: To compare the effect of ALA-PDT vs minocycline on rosacea. METHODS: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up. RESULTS: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT. LIMITATIONS: Limited sample size restricted us from drawing further conclusions. CONCLUSION: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea.


Asunto(s)
Fotoquimioterapia , Rosácea , Humanos , Ácido Aminolevulínico/efectos adversos , Minociclina/efectos adversos , Calidad de Vida , Fotoquimioterapia/efectos adversos , Rosácea/tratamiento farmacológico , Resultado del Tratamiento , Fármacos Fotosensibilizantes/efectos adversos
3.
Curr Treat Options Oncol ; 24(12): 1978-1993, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38095778

RESUMEN

OPINION STATEMENT: Non-melanoma skin cancer (NMSC) is a globally prevalent skin disease, with basal cell carcinoma and squamous cell carcinoma accounting for 99% of NMSC cases. While surgical excision is the most common approach, numerous non-surgical therapies have rapidly advanced in recent years. In cases of low-risk NMSC, alongside surgical excision, priority should be given to physical therapy and photodynamic therapy. Physical therapy modalities, exemplified by electrodessication and curettage, emerge as safe and efficacious alternatives. In juxtaposition, photodynamic therapy, albeit relatively more costly, assumes preference for patients exhibiting heightened cosmetic concerns owing to the scarring risks inherent to physical therapy and surgical excision. Notably, the combination of curettage and photodynamic therapy has exhibited remarkable efficacy in the treatment of nodular basal cell carcinoma. Additionally, for elderly patients who may be intolerant to stimulation, modified photodynamic therapy offers an almost painless option. When surgery is unavoidable, photodynamic therapy can be a valuable adjunct, allowing for a more conservative surgical approach, either before or after the procedure. Radiotherapy holds a prominent role in comprehensive treatment strategies, especially for patients ineligible for surgical intervention or those with lesions precluding further surgical measures. In cases of NMSC exhibiting perineural invasion or lymphovascular involvement, adjunctive radiotherapy is advised; however, potential adverse effects necessitate careful consideration. For advanced NMSC cases where surgery and physical therapy fall short, immunotherapy provide viable solutions. Systemic therapy employing Hedgehog pathway inhibitors can be considered for patients with distant metastatic basal cell carcinoma, despite its low incidence, or individuals with locally advanced lesions who are not surgical candidates, or those encountering recurrences after resection and radiotherapy. However, close monitoring of disease progression and adverse reactions is crucial. In this evolving landscape of NMSC treatment, personalized and multidisciplinary approaches are key, ensuring optimal outcomes while prioritizing patient safety and satisfaction.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Anciano , Proteínas Hedgehog , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/tratamiento farmacológico , Carcinoma Basocelular/terapia , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Antineoplásicos/uso terapéutico
4.
Skin Res Technol ; 29(10): e13497, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37881057

RESUMEN

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant tumor with a high recurrence rate after surgery. However, the genetic and epigenetic alterations underlying its pathogenesis remain unknown. DNA methylation is an important epigenetic modification involved in many biological processes. METHODS: In this study, enzymatic methyl-sequencing (EM-seq) technique was used to investigate the landscape of genome-wide DNA methylation from three pairs of tumor tissues and adjacent tissues of patients with EMPD. Additionally, we conducted histopathological examinations to assess the expression of fatty acid-binding protein 5 (FABP5) in another three paired samples from EMPD patients. RESULTS: The cluster analysis showed the good quality of the samples. A differential methylation region (DMR) heat map was used to quantitatively characterize genome-wide methylation differences between tumors and controls. Global DNA methylation level is lower in EMPD tissue compared to matched controls, indicating that DNA methylation discriminates between tumor and normal skin. And the top hypomethylation gene on the promoter region in tumor tissues was FABP5 on chromosome 8 with 38.44% decreased median methylation. We next identified the expression of FABP5 in paired tumors and adjacent tissues in three additional patients with EMPD. Immunofluorescence results showed FABP5 highly expressed in tumor tissues and co-located with CK7, CK20 and EMA. GO and KEGG enrichment analysis showed DMR genes on promoter are mainly enriched in the calcium ion transport, GTPase mediated signal transduction, Rap1 signaling pathway and GnRH signaling pathway. CONCLUSION: Taken together, our findings provide the first description of the whole genome methylation map of EMPD and identify FABP5 as a pathogenic target of EMPD.


Asunto(s)
Enfermedad de Paget Extramamaria , Neoplasias Cutáneas , Humanos , Enfermedad de Paget Extramamaria/genética , Enfermedad de Paget Extramamaria/metabolismo , Enfermedad de Paget Extramamaria/patología , Metilación , Neoplasias Cutáneas/patología , Epigénesis Genética/genética , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo
5.
Lasers Surg Med ; 54(5): 804-812, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35066886

RESUMEN

BACKGROUND AND OBJECTIVES: Conventional ALA-PDT (C-PDT) has limited efficacy in cutaneous squamous cell carcinoma (cSCC), and there is obvious pain during treatment, which limits its clinical application. We sought to modify photodynamic therapy into a more painless and effective treatment. METHODS: We modified C-PDT by reducing the incubation time of the pro-sensitizer and increasing the light dose; we named this method modified ALA-PDT (M-PDT). We compared the pain response and curative effect between C-PDT and M-PDT in cSCC mouse models. Pain-related proteins were examined by western blot analysis and immunohistochemistry. Tumor progression-associated signaling pathways were analyzed by RNA-seq and western blot analysis. Reactive oxygen species (ROS) generation was measured with a ROS test kit and Microplate reader. RESULTS: M-PDT greatly reduced pain during treatment. Interestingly, when the cSCC tumor volume increased to 150-200 mm3 , M-PDT almost completely eliminated the tumors, while C-PDT did not. The better curative effect of M-PDT might be due to the stronger suppression of the Stat3, Erk1/2, and mTOR signaling pathways. Moreover, flow cytometry demonstrated that M-PDT could recruit CD8+ T cells to inhibit cSCC progression. Further investigation determined that the different mechanisms of C-PDT and M-PDT were related to more ROS generation induced by M-PDT. CONCLUSIONS: Our results suggest that M-PDT, which is more painless and effective than C-PDT, is expected to provide a solution for the treatment of cSCC.


Asunto(s)
Carcinoma de Células Escamosas , Fotoquimioterapia , Neoplasias Cutáneas , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Animales , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ratones , Dolor/tratamiento farmacológico , Dolor/etiología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Cutáneas/patología
6.
Exp Dermatol ; 30(7): 923-931, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33860562

RESUMEN

Acne vulgaris is a chronic inflammatory cutaneous disease. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is a novel and effective approach for severe acne vulgaris treatment. However, its specific treatment mechanism still remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT regulated intense inflammatory response in acne vulgaris. It appeared that ALA-PDT suppresses proliferation and lipid secretion of primary human sebocytes. Besides, ALA-PDT could up-regulate the expression of CXCL8 in vivo and in vitro, amplifying the inflammatory response by recruiting T cells, B cells, neutrophils and macrophages. We also found that ALA-PDT elevated the expression of CXCL8 via p38 pathway. SB203580, a p38 pathway inhibitor, decreased the expression of CXCL8 in sebocytes after ALA-PDT. These findings indicate that ALA-PDT amplifies the intense inflammatory response in the treatment of acne vulgaris via CXCL8. Our data decipher the mechanism of intense inflammatory response after ALA-PDT for acne vulgaris.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Interleucina-8/uso terapéutico , Ácidos Levulínicos/inmunología , Ácidos Levulínicos/uso terapéutico , Fotoquimioterapia , Ensayo de Inmunoadsorción Enzimática , Humanos , Reacción en Cadena de la Polimerasa , Ácido Aminolevulínico
7.
Exp Cell Res ; 383(1): 111448, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31152706

RESUMEN

Low-intensity pulsed ultrasound (LIPUS) is a noninvasive therapeutic method which gradually being used in clinic including cancers. Exosomes mediate intercellular communication functions in disease development and the potential clinical applications in diagnosis and therapy. However, few studies have discussed the relationship between LIPUS and exosomes. Herein, we show that low intensity (0.6-2.1 W/cm2 or 0.6-3.4 W/cm2) LIPUS promoted exosomes secretion whereas higher intensity (3.4-5.0 W/cm2 or 5.0 W/cm2) LIPUS inhibited exosomes secretion, and this phenomenon is associated with autophagy. Pretreatment with 3-MA or down-regulation of LC3 potentiated low intensity LIPUS's promotion of exosomes secretion and conferred resistance to higher intensity LIPUS's effects on exosomes secretion. Furthermore, pretreatment with PP242 attenuated LIPUS-influenced exosomes secretion while expression of constitutively active Akt (Ad-myr-Akt) elevated LIPUS-influenced exosomes secretion, implying mTOR-dependent mechanism involved. The findings indicate that LIPUS influences exosomes secretion by targeting mTOR-mediated LC3 signaling in SPC-A1 and SPC-A1-BM cells. Our data provided initial evidence to connect LIPUS and secretion of exosomes, and highlight that LIPUS may be exploited in exosome-related diseases.


Asunto(s)
Autofagia , Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Neoplasias Pulmonares/patología , Ondas Ultrasónicas , Neoplasias Óseas/metabolismo , Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Exosomas/efectos de la radiación , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo
8.
Exp Cell Res ; 379(2): 203-213, 2019 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-30978341

RESUMEN

Tumor-derived exosomes contain informative microRNAs involved in carcinogenesis, cell migration, invasion and epithelial-mesenchymal transition (EMT), eventually contributing to metastasis of cancers. This study aims to clarify which and how exosomal miRNA affects tumor carcinogenesis and metastasis. Among them, miR-499a-5p was upregulated in both highly metastatic lung cancer cell line and their exosomes. MiR-499a-5p overexpression promoted cell proliferation, migration and EMT, while miR-499a-5p knockdown suppressed these processes in vitro. Inhibition of miR-499a-5p by antagomirs administration restrained tumor growth in vivo. Consequently, miR499a-sufficient exosomes, derived from highly metastatic cell line, enhanced cell proliferation, migration and EMT via mTOR pathway, and the effect could be inhibited by miR-499a-5p inhibitor. The study reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-499a-5p, and sheds a new insight on a novel molecular mechanism which modulates metastasis.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Línea Celular Tumoral , Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/patología
10.
J Cell Physiol ; 233(1): 516-529, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28300280

RESUMEN

B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1, and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor or rictor enhanced rapamycin's suppression of hsBAFF-induced survivin expression and proliferation/viability in B cells. Also, PP242, an mTORC1/2 kinase inhibitor, repressed survivin expression, and cell proliferation/viability more potently than rapamycin (mTORC1 inhibitor) in B cells in response to hsBAFF. Of interest, ectopic expression of constitutively active Akt (myr-Akt) or constitutively active S6K1 (S6K1-ca), or downregulation of 4E-BP1 conferred resistance to rapamycin's attenuation of hsBAFF-induced survivin expression and B-cell proliferation/viability, whereas overexpression of dominant negative Akt (dn-Akt) or constitutively hypophosphorylated 4E-BP1 (4EBP1-5A), or downregulation of S6K1, or co-treatment with Akt inhibitor potentiated the inhibitory effects of rapamycin. The findings indicate that rapamycin attenuates excessive hsBAFF-induced cell proliferation/survival via blocking mTORC1/2 signaling in normal and neoplastic B-lymphoid cells. Our data underscore that rapamycin may be a potential agent for preventing excessive BAFF-evoked aggressive B-cell malignancies and autoimmune diseases.


Asunto(s)
Antineoplásicos/farmacología , Factor Activador de Células B/metabolismo , Linfocitos B/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Linfoma de Células B/tratamiento farmacológico , Complejos Multiproteicos/metabolismo , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Linfocitos B/enzimología , Linfocitos B/patología , Proteínas de Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica , Humanos , Linfoma de Células B/genética , Linfoma de Células B/patología , Diana Mecanicista del Complejo 1 de la Rapamicina , Diana Mecanicista del Complejo 2 de la Rapamicina , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transfección
13.
J Ultrasound Med ; 36(3): 639-647, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28150376

RESUMEN

OBJECTIVES: A sonographic study was conducted to determine the prevalence of atherosclerosis across multiple arterial beds in an elderly Chinese population and to examine relationships between detected atherosclerosis and traditional risk factors. METHODS: A total of 197 participants underwent sonography of the abdominal aorta and bilateral carotid, femoral, and lower limb arteries. Images were reviewed to determine the presence or absence of plaques in each artery. Plaque thickness was measured as the indicator of plaque burden. Plaque prevalence was estimated per site and correlated with age, sex, and the Framingham Risk Score (FRS). Plaque frequency and thickness were compared between different arterial beds. RESULTS: Of the 197 participants (54% female; age range, 58-86 years), 90% had plaques present in at least 1 artery, and 55% had plaques present in at least 4 arteries. The most common sites for plaques were the carotid arteries (80%), followed by the lower limb arteries (59%), femoral arteries (57%), and abdominal aorta (37%). Plaque prevalence in each arterial bed except the abdominal aorta was significantly associated with male participants (P < .05), increasing age (P < .003) and FRS (P < .04). Male participants were more likely to have carotid (P = .04), femoral (P = .045), and lower limb (P = .006) plaques than female participants, but there was no significant difference in aortic plaque prevalence between male and female participants (P = .9). CONCLUSIONS: Plaque prevalence increased significantly in the carotid and peripheral arteries with increasing FRS. These findings should be considered for designing screening programs for stroke and heart attack prevention.


Asunto(s)
Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Ultrasonografía/métodos , Anciano , Anciano de 80 o más Años , Aorta Abdominal/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , China/epidemiología , Femenino , Arteria Femoral/diagnóstico por imagen , Evaluación Geriátrica/estadística & datos numéricos , Humanos , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Prevalencia , Medición de Riesgo , Factores de Riesgo , Factores Sexuales
14.
Cytokine ; 84: 37-46, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27235588

RESUMEN

B-cell activating factor of the TNF family (BAFF) has been documented to act as a critical factor in the development of aggressive B lymphocytes and autoimmune diseases. However, the effect of various cytokines on BAFF-elicited neoplastic B-lymphoid cells is not known. In this study, we exhibited that administration of human soluble BAFF (hsBAFF), IL-2, IL-4, IFN-γ, or TNF-α alone increased cell viability and survival in Raji cells concentration-dependently, yet a more robust viability/survival was seen in the cells co-treatment of IL-2, IL-4, IFN-γ, or TNF-α with hsBAFF, respectively. Further research revealed that both Erk1/2 and S6K1 signaling pathways were essential for IL-2, IL-4, IFN-γ, or TNF-α enhancement of the viability/survival in the hsBAFF-stimulated cells, as inhibition of Erk1/2 with U0126 or down-regulation of Erk1/2, or blockage of S6K1 with rapamycin or silencing S6K1, or silencing S6K1/Erk1/2, respectively, reduced the cell viability/survival in the cells treated with/without hsBAFF±IL-2, IL-4, IFN-γ, or TNF-α. These findings indicate that IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability/survival by activating Erk1/2 and S6K1 signaling in neoplastic B-lymphoid cells. Our data suggest that modulation of IL-2, IL-4, IFN-γ and/or TNF-α levels, or inhibitors of Erk1/2 or S6K1 may be a new approach to prevent BAFF-induced aggressive B-cell malignancies.


Asunto(s)
Factor Activador de Células B/metabolismo , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Linfocitos B/metabolismo , Línea Celular Tumoral , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Regulación hacia Abajo/fisiología , Humanos , Linfocitos/metabolismo , Transducción de Señal/fisiología
15.
Cell Mol Life Sci ; 72(24): 4867-84, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26118661

RESUMEN

B-cell activating factor (BAFF) is involved in not only physiology of normal B cells, but also pathophysiology of aggressive B cells related to malignant and autoimmune diseases. Rapamycin, a lipophilic macrolide antibiotic, has recently shown to be effective in the treatment of human lupus erythematosus. However, how rapamycin inhibits BAFF-stimulated B-cell proliferation and survival has not been fully elucidated. Here, we show that rapamycin inhibited human soluble BAFF (hsBAFF)-induced cell proliferation and survival in normal and B-lymphoid (Raji and Daudi) cells by activation of PP2A and inactivation of Erk1/2. Pretreatment with PD98059, down-regulation of Erk1/2, expression of dominant negative MKK1, or overexpression of wild-type PP2A potentiated rapamycin's suppression of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1, inhibition of PP2A by okadaic acid, or expression of dominant negative PP2A attenuated the inhibitory effects of rapamycin. Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin's effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. The findings indicate that rapamycin inhibits BAFF-stimulated cell proliferation/survival by targeting mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells. Our data highlight that rapamycin may be exploited for preventing excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.


Asunto(s)
Factor Activador de Células B/fisiología , Linfocitos B/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/fisiología , Animales , Factor Activador de Células B/metabolismo , Linfocitos B/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Humanos , Ratones , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Células Tumorales Cultivadas
16.
J Clin Rheumatol ; 22(2): 71-4, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26906298

RESUMEN

BACKGROUND: Osteoporosis is a common complication in patients with rheumatoid arthritis (RA). The change of bone mineral density (BMD) in patients with RA is slow, and little data are known about the long-term change of BMD. OBJECTIVES: This study aimed to determine the frequency of osteoporosis and the long-term change on BMD in a cohort of Chinese patients with RA routinely receiving calcium and vitamin D supplementation. METHODS: A total of 304 consecutive patients with RA were recruited. Bone mineral density measurements of the forearm, lumbar spine, and total hip were performed by dual-energy x-ray absorptiometry and compared with 200 age- and sex-matched healthy controls. Risk factors were analyzed by logistic regression models. RESULTS: The prevalence of osteoporosis at all measured sites in patients with RA was statistically significantly higher than in healthy controls. A total of 107 patients of the cohort had a mean of 4 years of follow-up. More patients with BMD decrease were found without calcium and vitamin D use compared with those who continuously took calcium and vitamin D (64.3% vs 19.8% at the forearm and 28.6% vs 16.1% at the total hip, respectively). Only the use of calcium and vitamin D supplementation was associated with a decreased risk of BMD decrease both at the forearm and at the total hip. CONCLUSIONS: Osteoporosis is common in Chinese patients with RA. Routine use of calcium and vitamin D supplementation decreased the risk of BMD decrease and should be recommended for all patients with RA.


Asunto(s)
Artritis Reumatoide/metabolismo , Densidad Ósea/fisiología , Osteoporosis/prevención & control , Absorciometría de Fotón , Adulto , Anciano , Artritis Reumatoide/tratamiento farmacológico , Pueblo Asiatico , Calcio/uso terapéutico , Suplementos Dietéticos , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Vitamina D/uso terapéutico
17.
Clin Exp Rheumatol ; 33(4): 465-70, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25962324

RESUMEN

OBJECTIVES: The objective of this study was to assess the prevalence and risk factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS). METHODS: Demographic and clinical data of 504 AS patients were collected. Bone mineral density (BMD) measurements of the lumbar spine, proximal femur and forearm were performed by dual-energy x-ray absorptiometry at baseline and follow-up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal controls. RESULTS: In contrast to normal controls, AS patients displayed a higher prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The prevalence of OP was significantly higher and the BMD were significantly lower in patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at the lumbar spine; Male gender, older age, hip involvement and lack of regular treatment were risk factors for bone loss at the femur. 173 cases were followed up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in annual BMD change between patients treated with or without low dose glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but not GCs treatment, were associated with decreased BMD at both the lumbar spine and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS: High disease activity and hip involvement are risk factors of bone loss in patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.


Asunto(s)
Glucocorticoides/uso terapéutico , Osteoporosis , Espondilitis Anquilosante , Absorciometría de Fotón/métodos , Adolescente , Adulto , Sedimentación Sanguínea , Densidad Ósea/efectos de los fármacos , Proteína C-Reactiva/análisis , China/epidemiología , Progresión de la Enfermedad , Femenino , Fémur/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Osteoporosis/sangre , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Osteoporosis/etiología , Osteoporosis/fisiopatología , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/epidemiología
18.
Artículo en Zh | MEDLINE | ID: mdl-25511267

RESUMEN

OBJECTIVE: To analyze the relationship between the pathological features and 64-multislice spiral computed tomography (64-MSCT) findings of pulmonary nodules in autopsies from patients with coal workers' pneumoconiosis (CWP), to investigate the optimal imaging method for the distribution of pulmonary nodules, and to provide data for the establishment of CT diagnostic criteria for CWP. METHODS: Cadaveric lung specimens were collected from 7 CWP patients. All of them were men, aged 42∼77 years (mean, 60.00±13.00 years), and their dust exposure time was 5∼30 years (mean, 15.4±8.01 years). The cadaveric lung specimens were treated by aeration, sectioning, and immobilization and were then examined by coronary 64-MSCT. The primitive images were reconstructed into the maximumintensity projection (MIP) images (slice thickness: 3 mm, 5 mm, and 8 mm). The sensitivities of imaging methods with different slice thickness were evaluated based on the pathology and anatomy of local pulmonary nodules, and the correlation between pathological results and radiological findings was analyzed. RESULTS: There were significant differences between the stages determined by pathological examination and high-kV chest radiography (before death) (χ(2) = 4.667, P < 0.05; kappa value = 0.167, P < 0.05). A total of 271 nodules were found in all pathological sections, including peribronchovascular nodules (27, 9.9%), centrilobular nodules (67, 24.6%), interlobular nodules (65, 24.3%), nodules within 5 mm from the pleura (45, 16.5%), pleural plaque-like nodules on the lateral chest wall (45, 16.5%), and nodules on the interlobar pleura (22, 8.1%). The likelihood ratio was the highest (0.981) between 5-mm MIP images and pathological results according to the chi-square test. CONCLUSION: The stage of pulmonary nodules determined by pathological examination is significantly different from that determined by high-kV chest radiography. The 5-mm MIP images of 64-MSCT provide a good reflection of the local pathology and anatomy of pulmonary nodules in CWP patients.


Asunto(s)
Antracosis/patología , Minas de Carbón , Pulmón/patología , Anciano , Carbón Mineral , Polvo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Pleurales/patología , Tomografía Computarizada Espiral
19.
Heliyon ; 10(7): e28942, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38601678

RESUMEN

Ferroptosis is an iron-dependent programmed cell death modality, which has showed great potential in anticancer treatment. Photodynamic therapy (PDT) is widely used in clinic as an anticancer therapy. PDT combined with ferroptosis-promoting therapy has been found to be a promising strategy to improve anti-cancer therapy efficacy. Fenton reaction in ferroptosis can provide oxygen for PDT, and PDT can produce reactive oxygen species for Fenton reaction to enhance ferroptosis. In this review, we briefly present the importance of ferroptosis in anticancer treatment, mechanism of ferroptosis, researches on PDT induced ferroptosis, and the mechanism of the synergistic effect of PDT and ferroptosis on cancer killing.

20.
Eur J Gastroenterol Hepatol ; 36(10): 1202-1208, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38973513

RESUMEN

BACKGROUND: Patients with cirrhosis commonly undergo endoscopic cyanoacrylate injection for gastric and esophageal variceal bleeding. However, postoperative infections can increase the risk of rebleeding and mortality. AIM: This study aimed to determine the risk of postoperative infections and its associated factors following cyanoacrylate injection treatment in these patients. METHODS: A retrospective analysis was conducted on 57 patients treated with ligation (ligation group), 66 patients treated with cyanoacrylate injection (injection group), and 91 patients treated with conservative treatment (control group) at the Nanchong Central Hospital. RESULTS: The rate of postoperative infection was similar among the cyanoacrylate, ligation, and conservative treatment groups, with no significant statistical difference observed ( P  = 0.97). Multivariate analysis identified postoperative Child-Pugh score and renal insufficiency as two independent risk factors for postoperative infection. The rebleeding rate in the injection group was significantly lower than in the other groups ( P  = 0.01). Mortality was significantly higher in the control group compared with the ligation and injection groups ( P  = 0.01). CONCLUSION: Cyanoacrylate combined with lauromacrogol injection did not significantly increase the risk of infection compared with ligation and conservative treatments, and it was more effective in reducing the risk of rebleeding. This method is safe, effective, and holds clinical value for broader application.


Asunto(s)
Cianoacrilatos , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Recurrencia , Humanos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Masculino , Femenino , Estudios Retrospectivos , Cianoacrilatos/efectos adversos , Cianoacrilatos/administración & dosificación , Cianoacrilatos/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Ligadura , Anciano , Resultado del Tratamiento , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Adulto , Infección de la Herida Quirúrgica/etiología , Cirrosis Hepática/complicaciones
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