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The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12 months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6 months of follow-up. The elimination rate increased to 69.6% (39/56) within 12 months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12 months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6 months (p < 0.001) and histologic regression within 12 months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.
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Ácido Aminolevulínico , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Femenino , Fotoquimioterapia/métodos , Ácido Aminolevulínico/uso terapéutico , Ácido Aminolevulínico/administración & dosificación , Adulto , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Displasia del Cuello del Útero/tratamiento farmacológico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Adulto Joven , AncianoRESUMEN
Non-small-cell lung cancer (NSCLC) is one of the deadliest cancers worldwide, and metastasis is considered one of the leading causes of treatment failure in NSCLC. Wnt/ß-catenin signaling is crucially involved in epithelial-mesenchymal transition (EMT), a crucial factor in promoting metastasis, and also contributes to resistance developed by NSCLC to targeted agents. Frizzled-7 (Fzd7), a critical receptor of Wnt/ß-catenin signaling, is aberrantly expressed in NSCLC and has been confirmed to be positively correlated with poor clinical outcomes. SHH002-hu1, a humanized antibody targeting Fzd7, was previously successfully generated by our group. Here, we studied the anti-tumor effects of SHH002-hu1 against NSCLC and revealed the underlying mechanism. First, immunofluorescence (IF) and near-infrared (NIR) imaging assays showed that SHH002-hu1 specifically binds Fzd7+ NSCLC cells and targets NSCLC tissues. Wound healing and transwell invasion assays indicated that SHH002-hu1 significantly inhibits the migration and invasion of NSCLC cells. Subsequently, TOP-FLASH/FOP-FLASH luciferase reporter, IF, and western blot assays validated that SHH002-hu1 effectively suppresses the activation of Wnt/ß-catenin signaling, and further attenuates the EMT of NSCLC cells. Finally, the subcutaneous xenotransplanted tumor model of A549/H1975, as well as the popliteal lymph node (LN) metastasis model, was established, and SHH002-hu1 was demonstrated to inhibit the growth of NSCLC xenografts and suppress LN metastasis of NSCLC. Above all, SHH002-hu1 with selectivity toward Fzd7+ NSCLC and the potential of inhibiting invasion and metastasis of NSCLC via disrupting Wnt/ß-catenin signaling, is indicated as a good candidate for the targeted therapy of NSCLC.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anticuerpos/farmacología , Antineoplásicos/farmacología , beta Catenina/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Vía de Señalización WntRESUMEN
OBJECTIVES: To summarize the clinical characteristics of glomus tympanicum tumors, and to explore the surgical methods and the strategy for auditory protection. METHODS: Ten cases (ears) of glomus tympanicum tumors were collected from the Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University from August 2014 to February 2022. All patients underwent endoscopic or microscopic surgery to achieve total removal of the tumor, followed up for 3 months to 8 years. We summarized and analyzed its clinical characteristics, compared the preoperative and postoperative hearing levels of patients, and made a retrospective summary of the surgical methods and the strategy for auditory protection. RESULTS: Ten patients were all female at (49.50±8.00) years old. Their medical history ranged from 15 days to 6 years. Seven patients complained of pulsatile tinnitus, and 80% (8/10) of the affected ears suffered different degrees of hearing loss. According to the modified Fisch & Mattox classification of glomus tympanicum tumors, 3 ears (30%) of 10 ears were A1, 2 ears (20%) were A2 and 5 ears (50%) were B1. In all 10 cases (ears), hearing was improved in 3 cases, bone gas conductance was maintained in 6 cases, and hearing was slightly decreased in 1 case. The difference of bone gas conductance was 0-10 dB in 7 cases (ears) after operation, and 10-20 dB in 3 cases (ears). There was no significant difference in the average air conduction hearing threshold, bone conduction hearing threshold and air-bone conduction difference between before and after operation (all P>0.05). All cases had no postoperative complications, and the external auditory canal and the incision behind the ear healed well. There was no recurrence after follow-up. CONCLUSIONS: Glomus tympanicum tumor is easy to bleed, so it is a challenge for total tumor resection and hearing function protection during operation. For type A and type B1 tumors, they can be completely removed under the condition of keeping the tympanic membrane and the ossicular chain. At the same time, the postoperative hearing function can be preserved, and even the hearing can be improved.
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Tumor del Glomo Timpánico , Humanos , Femenino , Adulto , Persona de Mediana Edad , Tumor del Glomo Timpánico/cirugía , Tumor del Glomo Timpánico/complicaciones , Tumor del Glomo Timpánico/patología , Estudios Retrospectivos , Resultado del Tratamiento , Endoscopía , Complicaciones PosoperatoriasRESUMEN
Aqueous zinc ion hybrid capacitors (aZHCs) are of great potential for large-scale energy storage and flexible wearable devices, of which the specific capacity and energy density need to be further enhanced for practical applications. Herein, a urea-mediated foaming strategy is reported for the efficient synthesis of monoliths consisting of nitrogen-enriched mesoporous carbon nanosheets (NPCNs) by prefoaming drying a solution made of polyvinylpyrrolidone, zinc nitrate, and urea at low temperatures, foaming and annealing at high temperatures, and subsequent acid etching. NPCNs have a large lateral size of ≈40 µm, thin thickness of ≈55 nm, abundant micropores and mesopores (≈3.8 nm), and a high N-doping value of 9.7 at.%. The NPCNs as the cathode in aZHCs provide abundant zinc storage sites involving both physical and chemical adsorption/desorption of Zn2+ ions, and deliver high specific capacities of 262 and 115 mAh g-1 at 0.2 and 10 A g-1 , and a remarkable areal capacity of ≈0.5 mAh cm-2 with a mass loading of 5.3 mg cm-2 , outperforming most carbon cathodes reported thus far. Moreover, safe and flexible NPCNs based quasi-solid-state devices are fabricated, which can withstand drilling and mechanical bending, suggesting their potential applications in wearable devices.
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Carbono , Suministros de Energía Eléctrica , Iones , Nitrógeno , Urea , ZincRESUMEN
OBJECTIVES: To assess the feasibility of preoperative ultrasound (US)-guided incisional biopsy through a prospective controlled clinical trial. METHODS: This was a prospective, double-arm, single-center study of Chinese patients. Thirty patients were enrolled in the study. Fourteen patients received incisional biopsies for which the choice of biopsy area relied on a clinical evaluation, and 16 patients received incisional biopsies for which the choice of biopsy area relied on a US-guided evaluation. The following procedure was used in the US-guided incisional biopsy group: 1) clinical and dermoscopic evaluation of skin lesions; 2) US examination; 3) incisional biopsy; 4) surgical excision; and 5) histopathological examination. The same procedure was used in the non-US-guided group except without US examination. RESULTS: In the non-US-guided group, the mean tumor thicknesses obtained from incisional biopsy and postoperative histopathological examination were 2.1 and 4.1 mm, respectively. Seven melanomas were underestimated by incisional biopsy, resulting in margins narrower than currently recommended. In the US-guided group, the mean tumor thicknesses obtained from US, incisional biopsy, and postoperative histopathological examination were 3.4, 2.9, and 2.7 mm, respectively. In only 3 melanomas was the tumor thickness of the incisional biopsy less than that of the postoperative histopathological examination, demonstrating that US-guided biopsy obtains the maximum thickness area. CONCLUSIONS: Preoperative US-guided incisional biopsy can enhance the pathological accuracy of incisional biopsy, which may allow us to better perform surgical excision with safe peripheral surgical margins.
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Melanoma , Neoplasias Cutáneas , Humanos , Biopsia , China , Biopsia Guiada por Imagen , Melanoma/diagnóstico por imagen , Melanoma/cirugía , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Ultrasonografía Intervencional , Melanoma Cutáneo MalignoRESUMEN
Non-melanoma skin cancer (NMSC) is the most common malignancy. Photodynamic therapy (PDT) is effective for the treatment of certain NMSCs. However, the clinical response rates of some NMSCs to single PDT are still far from ideal. The reason may be that PDT has shown limited efficacy in managing thicker NMSCs. To explore the efficacy and safety of dermabrasion combined with PDT (D-PDT) for the treatment of NMSCs. This was a retrospective, single-arm, multi-centre study. In total, 172 tumours from 40 patients were treated with D-PDT during the study period. The mean follow-up period was 40 months (range 15-110 months). D-PDT was performed with 633-nm red light at 80 m W/cm2 after lesion dermabrasion and 4 h of photosensitizer exposure. Six nodular basal cell carcinomas (nBCCs) from 6 patients, 9 squamous cell carcinomas (SCCs) from 9 patients, 17 Bowen diseases (BDs) from 10 patients and 140 actinic keratoses (AKs) from 15 patients treated with D-PDT were examined in this study. Only two patients with three AKs experienced recurrence over 12 months. The mean final follow-up periods of patients with AKs, BDs, nBCCs and SCCs were 30, 33, 45 and 60 months, respectively. Thirty-four of the 40 patients treated with D-PDT reported excellent or good cosmetic results. The mean Dermatology Life Quality Index (DLQI) scores of the patients improved significantly after treatment (estimated MD 9.72 [95% CI 8.69 to 10.75]; p < 0.001). D-PDT is a safe, cosmetic and effective treatment that could be a new candidate therapeutic for NMSC.
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Queratosis Actínica , Fotoquimioterapia , Neoplasias Cutáneas , Ácido Aminolevulínico/uso terapéutico , Dermabrasión , Humanos , Queratosis Actínica/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: This study aimed to determine the risk factors associated with early postoperative complications of trans-canal endoscopic ear surgery (TEES), then to develop a risk index. MATERIALS AND METHODS: This single-institution retrospective study reviewed TEESs from January 1, 2017, to December 31, 2019 in a tertiary hospital. In the derivation cohort, univariable and multivariable logistic regression were performed to identify factors significantly associated with early postoperative complications of TEES. Then these parameters were integrated into a trans-canal endoscopic ear surgery risk index (TEESRI). The performance of TEESRI was compared with that of the American Society of Anesthesiologists (ASA) classification using the validation cohort. RESULTS: 932 TEESs were enrolled in total and 151 (16.2%) developed early postoperative complications. In the derivation set, 8 factors including state of the opposite ear and presence of nasal or pharyngeal diseases were found to be independently associated with the occurrence of early postoperative complications on multivariable regression analysis [area under the curve (AUC), 0.806; 95% confidence interval (CI), 0.765-0.848]. Using the validation cohort, the AUC of the TEESRI was 0.776 [95%CI, 0.711-0.842], with a sensitivity of 82.2% and specificity of 65.5%, while the AUC of the ASA classification was 0.512 (95%CI, 0.421-0.603). The TEESRI outperformed the ASA classification when evaluating the risk for early postoperative complications of TEES. CONCLUSIONS: Based on the 8 risk factors, the TEESRI was established with satisfactory predicting capacity. Surgeons should pay extra attention to the risk factors in the TEESRI, when treating patients.
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Procedimientos Quirúrgicos Otológicos , Endoscopía/efectos adversos , Humanos , Procedimientos Quirúrgicos Otológicos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2-dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct-acting antiviral (DAA) therapy. METHODS: Patients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. RESULTS: A total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase-to-platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two-dimensional SWE and TE were strongly correlated (r = 0.885-0.897; P < .001). Albumin and the baseline liver stiffness measurement were independent factors of liver stiffness measurement changes after DAA therapy. CONCLUSIONS: Direct-acting antiviral therapy can significantly decrease liver stiffness (using both 2D SWE and TE) but not SWD and ATI values in patients with hepatitis C. An increased CAP is also observed after DAA therapy.
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Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Photodynamic therapy (PDT) is widely used in skin diseases; the response rate of PDT treatment varies widely. The limited penetration in the tissue of photosensitizers influenced the penetration depth of PDT, which obviously impacts the therapeutic effect. The studies have improved the efficacy of PDT through various pretreatment applications; especially, the physical pretreatment had achieved significant outcomes. We will review the physical pretreatment to optimize the efficacy of PDT in skin diseases by searching the literature on this topic. The types of physical pretreatment commonly used in the clinical practice are discussed: curettage, superficial shaving, laser, surgical resection, plum-blossom needles, and microneedles. Compared with PDT alone, the physical pretreatment before PDT application was generally improved the efficacy and reduced the recurrence, especially in actinic keratoses (AK), Bowen disease (BD), basal cell carcinoma (BCC), and viral warts. The application of the physical pretreatments before PDT may improve the efficacy of PDT in various skin diseases. However, each kind of physical pretreatment has the benefit and shortcoming, and the applicable situation is different.
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Queratosis Actínica , Fotoquimioterapia , Enfermedades de la Piel , Neoplasias Cutáneas , Ácido Aminolevulínico/uso terapéutico , Humanos , Queratosis Actínica/tratamiento farmacológico , Recurrencia Local de Neoplasia , Fármacos Fotosensibilizantes/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: In the first year of dialysis, patients are vulnerable to cardiovascular disease (CVD) hospitalization, but knowledge regarding the risk factors and long-term outcomes of cardiovascular readmission within the first year after dialysis in incident continuous ambulatory peritoneal dialysis (CAPD) patients is limited. METHODS: This retrospective cohort study was conducted in incident CAPD patients. The demographic characteristics, laboratory parameters, and CVD readmission were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included CVD mortality, infection-related mortality and technique failure. A logistic regression was used to identify the risk factors associated with CVD readmission within the first year after dialysis. Cox proportional hazards models were used to evaluate the association between CVD readmission and the outcomes. RESULTS: In total, 1589 peritoneal dialysis (PD) patients were included in this study, of whom 120 (7.6%) patients had at least one episode of CVD readmission within the first year after dialysis initiation. Advanced age, CVD history, and a lower level of serum albumin were independently associated with CVD readmission. CVD readmission within the first year after dialysis was significantly associated with all-cause (HR 2.66, 95%CI 1.91-3.70, p < 0.001) and CVD (HR 3.42, 95%CI 2.20-5.31, p < 0.001) mortality, but not infection-related mortality or technique failure, after adjusting for confounders. CONCLUSIONS: Our findings suggest that an advanced age, a history of CVD, and a lower level of serum albumin were independently associated with CVD readmission. Moreover, CVD readmission was associated with all-cause and cardiovascular mortality in incident CAPD patients.
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Enfermedades Cardiovasculares/mortalidad , Fallo Renal Crónico/terapia , Readmisión del Paciente/estadística & datos numéricos , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/mortalidad , Adulto , Factores de Edad , Anciano , Enfermedades Cardiovasculares/etiología , Causas de Muerte , China/epidemiología , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Factores de TiempoRESUMEN
Homozygous or compound heterozygous mutations of the ß-globin gene lead to ß-thalassemia (ß-thal) major (ß-TM) or ß-thal intermedia (ß-TI), whereas heterozygotes usually show microcytosis with negligible or no hemolysis. Certain missense mutations in exon 3, however, produce unstable globins causing a dominant ß-thal phenotype or hemolytic anemia in heterozygotes. Here we report a mutation in exon 3 of the ß-globin gene, which results in an unstable globin (Hb Dieppe) [ß127(H5)GlnâArg; HBB: c.383A>G] with a dominant ß-thal phenotype in two generations of a Chinese family. Physicians should be alerted to this mechanism of ß-thal considering its relative rarity.
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Talasemia beta , Exones , Humanos , Mutación , Fenotipo , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genéticaRESUMEN
Removal of hexavalent chromium [Cr(VI)] from water was evaluated using a low-cost coated sand adsorbent for potential application in a flow-through filter system using permeable adsorption media. Manganese-aluminum coated sand (MACS) was investigated as a hybrid metal oxide based adsorbent due to the potential efficacy of manganese oxide and aluminum oxide for adsorption of Cr(VI) from water. Adsorbent characterization was performed using XRD, SEM/EDX, XPS and BET. Adsorption experiments were performed to determine adsorption capacity and kinetics. The effect of pH, common co-existing ions found in natural water, and the recyclability of adsorbent were investigated. Adsorbent characterization showed that the MACS sorbent contained aluminum oxide, manganese (III) oxide and manganese (IV) oxide. Adsorption followed the Langmuir and Freundlich adsorption equations, indicating favorable adsorption of Cr(VI) onto the MACS sorbent, while results from the Dubinin-Radushkevich equation were suggestive of physical adsorption of Cr(VI). Cr(VI) adsorption onto the MACS sorbent followed pseudo-second order kinetics. The adsorbent was effective in removing Cr(VI) over a broad pH range from 3 to 9.5, while surface charge analysis confirmed the adsorption of Cr(VI) onto the acidic surface of the MACS sorbent with a pHPZC of 9.72. The presence of co-existing ions bicarbonate, sulfate and phosphate in water resulted in a decrease in Cr(VI) uptake in the following order: phosphate > bicarbonate > sulfate. The presence of calcium resulted in a slight increase in Cr(VI) uptake. The MACS sorbent is a recyclable sorbent for adsorption and removal of Cr(VI) from water within 30 minutes of contact time.
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Aluminio/química , Cromo/química , Manganeso/química , Arena/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Adsorción , Concentración de Iones de Hidrógeno , Cinética , Compuestos de Manganeso/química , Concentración Osmolar , Óxidos/químicaRESUMEN
The M2 splice isoform of pyruvate kinase (PKM2) is a key enzyme for generating pyruvate and ATP in the glycolytic pathway, whereas the role of PKM2 in tumorigenesis remains a subject of debate. In our study, we found PKM2 is highly expressed in melanoma patients and the malignance is positively correlated with high PKM2 activity and glycolytic capability in melanoma cells. Suppression of PKM2 expression by knocking down markedly attenuated malignant phenotype both in vitro and in vivo, and restoration of PKM2 expression in PKM2 depleted cells could rescue melanoma cells proliferation, invasion and metastasis. With the data indicating PKM2 as a potential therapeutic target, we performed screening for PKM2 inhibitors and identified benserazide (Ben), a drug currently in clinical use. We demonstrated that Ben directly binds to and blocks PKM2 enzyme activity, leading to inhibition of aerobic glycolysis concurrent up-regulation of OXPHOS. Of note, despite PKM2 is very similar to PKM1, Ben does not affect PKM1 enzyme activity. We showed that Ben significantly inhibits cell proliferation, colony formation, invasion and migration in vitro and in vivo. The specificity of Ben was demonstrated by the findings that, suppression of PKM2 expression diminishes the efficacy of Ben in inhibition of melanoma cell growth; ectopic PKM2 expression in normal cells sensitizes cells to Ben treatment. Interestingly, PKM2 activity and aerobic glycolysis are upregulated in BRAFi-resistant melanoma cells. As a result, BRAFi-resistant cells exhibit heightened sensitivity to suppression of PKM2 expression or treatment with Ben both in vitro and in vivo.
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Benserazida/farmacología , Proteínas Portadoras/antagonistas & inhibidores , Melanoma/tratamiento farmacológico , Proteínas de la Membrana/antagonistas & inhibidores , Animales , Antineoplásicos/farmacología , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Glucólisis/efectos de los fármacos , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Terapia Molecular Dirigida , Invasividad Neoplásica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Hormonas Tiroideas/biosíntesis , Hormonas Tiroideas/genética , Hormonas Tiroideas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de Unión a Hormona TiroideRESUMEN
BACKGROUND: Melanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment. METHODS: We detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma. RESULTS: We found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis. CONCLUSIONS: Taken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment.
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Introduction: The aim of this retrospective study was to analyze the long-term outcomes and factors associated with treatment failure of Gamma Knife radiosurgery (GKRS) for postsurgical residual or recurrent nonfunctioning pituitary adenomas (NFPAs). Design and Methods: A total of 148 cases of postsurgical residual or recurrent NFPA patients were enrolled in the study. There were 111 cases with residual tumor and 37 cases with recurrent tumor. The median age was 46.0 years (Range: 10.9-75.8 years). The median tumor volume at GKRS was 3.6 cm3 (Range: 0.3-74.5 cm3), and the median tumor margin dose was 14.0 Gy (Range: 9 - 20 Gy). Results: Tumor shrunk in 111 patients (75%), remained stable in 17 patients (11.5%), and progressed in 20 patients (13.5%) during a median of 64.5 months (Range: 14.5 - 236.0 months) of imaging follow-up. The progression-free survival rates were 99%, 91%, 88% and 74% at 1, 3, 5 and 10 years after GKRS, respectively. In a multivariate analysis, tumor margin dose (<13 Gy) was significantly associated with tumor progression (hazard ratio=3.526, 95% confidence interval=1.400-8.877, p=0.007). New hypopituitarism occurred in 22 out of 80 patients (27.5%), including hypogonadism (n=7), hypothyroidism (n=9), hypocortisolism (n=15) and growth hormone deficiency (n=1). In univariate and multivariate analysis, there were no factors significantly associated with new hypopituitarism. Six patients (4.1%) developed new or worsening visual dysfunction. Four patients (2.7%) developed new cranial neuropathy. Conclusion: In this study, GKRS can offer a high tumor control rate as well as a low rate of complications in postsurgical residual or recurrent NFPA patients.
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Neoplasias Hipofisarias/cirugía , Radiocirugia/métodos , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Hipopituitarismo/diagnóstico por imagen , Hipopituitarismo/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/cirugía , Neoplasias Hipofisarias/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Vulvar intraepithelial neoplasia (VIN), a precancerous lesion, is difficult to treat by excision or ablation due to high recurrence rates. Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure and is now widely used to treat non-melanoma skin diseases. However, the clinical response rates of VIN to single PDT are unstable. The reason may be the limited light penetration into deep tissues. OBJECTIVE: To retrospectively evaluate the clinical response and recurrence of VIN after combined treatment with superficial shaving and PDT. STUDY DESIGN/MATERIALS AND METHODS: Seventeen patients with VIN were enrolled. All patients had multifocal high-grade VIN that had failed to respond to various therapies. Superficial shaving was performed only once and prior to the first 5-aminolaevulinic acid (5-ALA)-PDT cycle. Generally, the procedure of 5-ALA PDT for each patient was performed in three sessions. Clinical response, recurrence, cosmetic outcomes, adverse events, patient satisfaction, quality of life, and mental health were assessed. The expression of p16 and Ki-67 in pre- and post-treatment tissue was detected. RESULTS: A clinical response of 94% was observed in 17 patients, who were administered combination therapy, over an observation period of 12 months. Approximately, 71% of patients had excellent cosmetic outcomes. All patients had satisfactory therapeutic effects and significant improvements in quality of life and mental health. Downregulation of p16 and Ki-67 may have been correlated with recurrence after 5-ALA-PDT. CONCLUSION: Combined treatment with superficial shaving and 5-ALA-PDT is a safe and effective option for VIN. In particular, combination therapy is recommended for patients with large, multifocal, high-grade lesions; repeated recurrence; and strong willingness to maintain vulvar configuration and function. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/cirugía , Fotoquimioterapia , Neoplasias de la Vulva/tratamiento farmacológico , Neoplasias de la Vulva/cirugía , Adulto , Ácido Aminolevulínico/uso terapéutico , Carcinoma in Situ/patología , Femenino , Humanos , Persona de Mediana Edad , Satisfacción del Paciente , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vulva/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Plantar warts are a viral infectious lesion on the foot. The regression of plantar warts can be challenging despite the presence of a variety of available treatment modalities. Photodynamic therapy (PDT) has been recommended for the treatment of plantar warts. However, the effect of PDT in the treatment of plantar warts is not clear. Thus, we compared the efficacy of combining superficial shaving with PDT (SS-PDT) with that of cryotherapy in the treatment of recalcitrant plantar warts. STUDY DESIGN/MATERIALS AND METHODS: Forty-six patients with 271 warts received SS-PDT, and 26 patients with 147 warts received cryotherapy. For the SS-PDT group, the lesions were shaved in situ, and PDT was performed immediately. For the cryotherapy group, appropriate pressure was applied by freezing rod to fully freeze the lesion tissue. The overall clinical response effects, recurrence rates, adverse events, patient satisfaction and the quality of life were assessed. RESULTS: The SS-PDT group achieved a 91.3% success rate (defined as >50% on clearance) after treatment for 6 months, whereas only 23.1% of treatment in the cryotherapy group was successful. After 6 months of follow-up, the recurrence rate in the SS-PDT group was significantly lower than that in the cryotherapy group (8.7% vs. 76.9%, P < 0.001). The patients with SS-PDT were more satisfied with the treatment than the patients with cryotherapy (8.8 ± 1.4 vs. 4.9 ± 1.4, P < 0.001). Moderate pain was the main adverse event in SS-PDT, and cryotherapy may cause severe pain and blistering. CONCLUSIONS: Our results suggest that superficial shaving combined with PDT is promising as a safe and effective therapy for patients with plantar warts, especially for patients with multiple recalcitrant warts. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
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Fotoquimioterapia , Verrugas , Crioterapia , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Calidad de Vida , Verrugas/tratamiento farmacológicoRESUMEN
Introduction: Malignant germ cell tumors (MGCT) can occur in both genders. In this study, we present eight cases of mixed ovarian MGCT in patients. Most patients reported in the current study are young women, among whom clinical characteristics of gonadal dysgenesis associated MGCT were rarely reported.Methods: Comprehensive information of eight patients with mixed ovarian MGCTs, including patients' age, clinical features, tumor markers, imaging findings, surgical records, pathology, karyotyping tests, chemotherapy and follow-up were collected. Surgical specimens were evaluated by two specialized gynecologic pathologists.Results: All patients received surgery, while seven received chemotherapy. Among them, two received a second surgery and three patients received hormone replacement therapy (HRT) after gonadectomy. Four of five patients with amenorrhea were found to have 46, XY karyotype. All patients showed no sign of recurrence at the latest follow-up.Discussion: Karyotyping or genetics testing in patients with amenorrhea is necessary, especially for patients with pelvic mass, which can help surgeons to evaluate the necessity of gonadectomy before surgery. The patients with gonadal dysgenesis associated mixed ovarian MGCT seem to have better prognosis and long survival time. Thus, HRT, an option that can improve life quality, is worth considering for these patients after gonadectomy.
Asunto(s)
Disgenesia Gonadal/complicaciones , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias Ováricas/etiología , Adolescente , Adulto , Antineoplásicos/uso terapéutico , Femenino , Procedimientos Quirúrgicos Ginecológicos , Terapia de Reemplazo de Hormonas , Humanos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Ovario/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.