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2.
Mod Pathol ; 37(3): 100427, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219951

RESUMO

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.


Assuntos
Neoplasias de Bainha Neural , Neurilemoma , Humanos , Neurilemoma/patologia , Neoplasias de Bainha Neural/patologia , Transformação Celular Neoplásica , Proteínas Adaptadoras de Transporte Vesicular
4.
Medicina (Kaunas) ; 58(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36143860

RESUMO

Background and Objectives: Women with interstitial cystitis (IC) suffer from spontaneous serious bladder pain symptoms without immediate resolution. Women with IC may lack knowledge of how to help themselves. Therefore, a measurement of IC self-help and medical-resource-seeking for women with IC is needed. Materials and Methods: This study recruited 100 women with IC from a teaching hospital in Northern Taiwan. The reliability and validity of the Interstitial Cystitis Self-Help and Medical Resources Scale (ICSR) were assessed using expert validity, confirmatory factor analysis (CFA) to test the construct validity, composite reliability to evaluate the internal consistency, and item analysis to test the discrimination validity of each item. Results: The results showed that the ICSR had accurate goodness-of-fit indices and the component reliability ranged from 0.42 to 0.83, indicating good reliability and validity. Conclusions: The ICSR is recommended for screening the self-help and medical-resource-seeking abilities of women with IC to aid in diagnosing IC and providing more precise medical treatments.


Assuntos
Cistite Intersticial , Cistite Intersticial/diagnóstico , Cistite Intersticial/terapia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Reprodutibilidade dos Testes , Taiwan
5.
Arch Pathol Lab Med ; 146(9): 1084-1093, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902854

RESUMO

CONTEXT.­: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced, adverse T-cell-mediated hypersensitivity reaction that most often involves skin. The pathologic findings of DRESS-related lymphadenopathy have been described infrequently in the literature. OBJECTIVE.­: To present a case series of DRESS-related lymphadenopathy with an emphasis on the morphologic spectrum. DESIGN.­: We describe detailed clinical and pathologic findings along with the literature review. We focus on the differential diagnosis between DRESS lymphadenopathy and angioimmunoblastic T-cell lymphoma (AITL). RESULTS.­: There were 4 men and 1 woman with a mean age of 41 years (range, 23-59 years). One patient (20%) died. Three lymph node biopsy specimens showed a pattern reminiscent of AITL (AITL-like pattern) and 2 cases showed necrotizing lymphadenitis (Kikuchi-like pattern), associated with vasculitis in 1 case. The AITL-like morphology of DRESS-related lymphadenopathy may be difficult to distinguish from genuine AITL. The clinical information is important for differential diagnosis, including history of drug exposure, age, and the rarity or absence of AITL-associated manifestations such as hemolytic anemia and hypergammaglobulinemia. Molecular analysis of the T-cell receptor genes is helpful, typically revealing a polyclonal pattern in DRESS-related lymphadenopathy. CONCLUSIONS.­: In the literature, 4 histologic patterns of DRESS lymphadenopathy have been described: reactive lymphoid hyperplasia, necrotizing lymphadenitis, Hodgkin lymphoma-like, and AITL-like. These patterns, particularly those that resemble lymphoma, highlight the importance of correct diagnosis to avoid unnecessary therapies.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Linfadenopatia Imunoblástica , Linfadenite , Adulto , Diagnóstico Diferencial , Síndrome de Hipersensibilidade a Medicamentos/complicações , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/patologia , Feminino , Humanos , Linfadenopatia Imunoblástica/patologia , Linfadenite/complicações , Masculino
6.
Front Endocrinol (Lausanne) ; 12: 793431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899616

RESUMO

Technological advances in thyroid surgery have rapidly increased in recent decades. Specifically, recently developed energy-based devices (EBDs) enable simultaneous dissection and sealing tissue. EBDs have many advantages in thyroid surgery, such as reduced blood loss, lower rate of post-operative hypocalcemia, and shorter operation time. However, the rate of recurrent laryngeal nerve (RLN) injury during EBD use has shown statistically inconsistent. EBDs generate high temperature that can cause iatrogenic thermal injury to the RLN by direct or indirect thermal spread. This article reviews relevant medical literatures of conventional electrocauteries and different mechanisms of current EBDs, and compares two safety parameters: safe distance and cooling time. In general, conventional electrocautery generates higher temperature and wider thermal spread range, but when applying EBDs near the RLN adequate activation distance and cooling time are still required to avoid inadvertent thermal injury. To improve voice outcomes in the quality-of-life era, surgeons should observe safety parameters and follow the standard procedures when using EBDs near the RLN in thyroid surgery.


Assuntos
Monitorização Intraoperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Nervo Laríngeo Recorrente/cirurgia , Instrumentos Cirúrgicos/tendências , Tireoidectomia/tendências , Voz/fisiologia , Animais , Eletrocoagulação/efeitos adversos , Eletrocoagulação/tendências , Humanos , Complicações Pós-Operatórias/etiologia , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Instrumentos Cirúrgicos/efeitos adversos , Glândula Tireoide/inervação , Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos , Terapia por Ultrassom/tendências
7.
World J Gastroenterol ; 27(31): 5181-5188, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497443

RESUMO

Hepatitis C virus (HCV) reactivation occurs in 23% of HCV-infected cancer patients receiving chemotherapy. Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare. Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy. However, 26%-57% of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy, which results in deleterious changes in the cancer treatment plan. Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established, universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines. All the currently approved direct-acting antivirals (DAAs) can be used in cancer patients, but the use of DAAs during chemotherapy should avoid drug-drug interactions between chemotherapy and antiviral agents. If there are no contraindications or anticipated drug-drug interactions, DAAs treatment can be administered before, during, or after chemotherapy. In conclusion, HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy. An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy. Currently, universal HCV screening is recommended in hematological malignancy patients before chemotherapy, but there is no evidence-based guideline for other cancer patients. DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.


Assuntos
Hepatite B Crônica , Hepatite C Crônica , Hepatite C , Antivirais/efeitos adversos , Hepacivirus , Hepatite B Crônica/tratamento farmacológico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Exacerbação dos Sintomas , Ativação Viral
8.
J Viral Hepat ; 27(9): 873-879, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32301253

RESUMO

No guidelines have been developed for the management of HCV-infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = .003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV-infected haematological cancer patients was higher than that in those with HCC and non-HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P < .001 and P = .004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of haematological malignancy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hematológicas , Hepatite C , Neoplasias Hepáticas , Antivirais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/virologia , Hepatite C/complicações , Hepatite C/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Exacerbação dos Sintomas
9.
Low Urin Tract Symptoms ; 12(3): 183-189, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31970901

RESUMO

BACKGROUND: This study aims to investigate the self-perception of symptoms, medical help seeking, and self-help strategies of women with interstitial cystitis (IC). METHODS: A mixed method of qualitative and quantitative approaches was employed. The qualitative approach used in-depth interviews about the subjective experience of symptoms, medical help seeking, and self-help strategies for their IC. The quantitative inquiry was conducted by a yes or no response to the question "Did self-perceived severe symptoms of IC interfere with your daily life?" A loglinear model was applied to investigate the associations between possible factors. RESULTS: This study recruited 68 women aged 20 to 69 years, of whom 22 were interviewed for qualitative data. About 72.1% of the women responded that self-perceived severe IC symptoms interfered with their daily life. A significant negative association between employment and self-perceived severe IC symptoms (P < .05) was observed. Qualitative results revealed three important themes: (1) bothersome symptoms-all-day bladder pain and lower urinary tract symptoms and deteriorated quality of life, (2) medical help seeking-exhaustion and frustration, (3) self-help strategies-coexisting with IC or feeling helpless. CONCLUSIONS: IC women feel exhausted and frustrated by seeking medical attention for this incurable disease for a long time. IC women have troubled and uneasy daily lives. Being employed or engaging in activities can divert attention to alleviate symptoms. IC patient support groups allow patients to share their self-help experiences with interdisciplinary medical teams to provide physical and psychological treatment.


Assuntos
Cistite Intersticial/psicologia , Cistite Intersticial/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Autocuidado , Autoimagem , Adulto , Idoso , Dor Crônica/etiologia , Dor Crônica/psicologia , Emprego , Feminino , Frustração , Humanos , Pessoa de Meia-Idade , Qualidade de Vida
10.
J Vis Exp ; (144)2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30799841

RESUMO

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. In recent years, intraoperative neural monitoring (IONM) has been widely adapted as an adjunct technique to localize the RLN, detect RLN injury, and predict vocal cord function during the operations. Many studies have also used animal models to investigate new applications of IONM technology and to develop reliable strategies for preventing intraoperative RLN injury. The aim of this article is to introduce a standard protocol for using a porcine model in IONM research. The article demonstrates the procedures for inducing general anesthesia, performing tracheal intubation, and experimental design to investigate the electrophysiological characteristics of RLN injuries. Applications of this protocol can improve overall efficacy in implementing the 3R principle (replacement, reduction and refinement) in porcine IONM studies.


Assuntos
Traumatismos do Nervo Laríngeo Recorrente/etiologia , Nervo Laríngeo Recorrente/cirurgia , Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Animais , Humanos , Complicações Intraoperatórias , Modelos Animais , Suínos
11.
Am J Transl Res ; 11(12): 7492-7502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934296

RESUMO

To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.

12.
Thyroid ; 28(11): 1508-1516, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30255736

RESUMO

BACKGROUND: Intraoperative neural monitoring (IONM) has gained widespread acceptance as an adjunct to the gold standard of visual identification of the recurrent laryngeal nerve (RLN) during thyroid surgery. Currently, laryngeal electromyography (EMG) recording during IONM is almost always performed using endotracheal tube (ETT) surface electrodes placed adjacent to vocal folds originating from the inner surface of the thyroid cartilage (TC). Therefore, it was hypothesized that surface recording electrodes placed on the outer surface of the TC should enable access to the EMG response of the vocal folds during IONM. The aim of this experimental study was to evaluate the feasibility of the transcartilage approach for laryngeal EMG recording during IONM. METHODS: A porcine model (12 pigs and 24 RLN sides) with well established applicability in IONM research was used for the experiments. Both ETT electrodes adjacent to vocal folds and adhesive pre-gelled electrodes on the TC were used for EMG recording during IONM. Electrically evoked EMG signals detected by both electrode types were recorded and analyzed. EMG changes during tracheal displacement and RLN traction injury were compared. RESULTS: Both the ETT and TC recording electrodes recorded typical laryngeal EMG waveforms evoked by a 1 mA stimulus current applied on both sides of the RLNs and vagus nerves (VNs). Under RLN stimulation, the mean EMG amplitudes recorded with the ETT and TC electrodes were 973 ± 79 µV and 695 ± 150 µV, respectively. Under VN stimulation, the mean amplitudes were 841 ± 163 µV and 607 ± 162 µV, respectively. When upward displacement of the trachea was experimentally induced, the TC electrodes showed less variation in recorded EMG signals compared to ETT electrodes. When RLN traction stress was experimentally induced, both the ETT and TC electrodes accurately recorded the typical EMG pattern of progressively degrading amplitude and gradual recovery after release of traction. CONCLUSIONS: This study confirms the feasibility of using transcartilage surface electrodes for recording laryngeal EMG signals evoked during IONM in an animal model. However, before practical application of this approach in clinical thyroid surgery, further studies are needed to improve electrode designs by optimizing their shapes and sizes, and increasing their adhesive stability and sensitivity.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Animais , Eletromiografia , Estudos de Viabilidade , Modelos Animais , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Suínos
13.
Radiat Oncol ; 13(1): 45, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29554940

RESUMO

BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). RESULTS: Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2-3 vs. N0-1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3-4 (HR: 3.5, 95% CI: 1.0-12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001-1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. CONCLUSION: N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.


Assuntos
Carcinoma/patologia , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/métodos , Fatores de Risco , Adulto Jovem
14.
Cancer Manag Res ; 10: 131-141, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29403311

RESUMO

BACKGROUND: Patients treated with radiotherapy are at risk of developing a second cancer during their lifetime, which can directly impact treatment decision-making and patient management. The aim of this study was to qualify and compare the secondary cancer risk (SCR) after intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: We analyzed the treatment plans of a cohort of 10 NPC patients originally treated with IMRT or VMAT. Dose distributions in these plans were used to calculate the organ equivalent dose (OED) with Schneider's full model. Analyses were applied to the brain stem, spinal cord, oral cavity, pharynx, parotid glands, lung, mandible, healthy tissue, and planning target volume. RESULTS: We observed that the OED-based risks of SCR were slightly higher for the oral cavity and mandible when VMAT was used. No significant difference was found in terms of the doses to other organs, including the brain stem, parotids, pharynx, submandibular gland, lung, spinal cord, and healthy tissue. In the NPC cohort, the lungs were the organs that were most sensitive to radiation-induced cancer. CONCLUSION: VMAT afforded superior results in terms of organ-at-risk-sparing compared with IMRT. Most OED-based second cancer risks for various organs were similar when VMAT and IMRT were employed, but the risks for the oral cavity and mandible were slightly higher when VMAT was used.

15.
Am J Chin Med ; 46(1): 87-106, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29298513

RESUMO

oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent atherosclerosis.


Assuntos
Andrographis/química , Colesterol/metabolismo , Diterpenos/farmacologia , Células Espumosas/metabolismo , Lipoproteínas LDL/efeitos adversos , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Anti-Inflamatórios , Antineoplásicos Fitogênicos , Antioxidantes , Aterosclerose/etiologia , Transporte Biológico/genética , Antígenos CD36/genética , Antígenos CD36/metabolismo , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Receptores X do Fígado/fisiologia , Camundongos , RNA Mensageiro/metabolismo , Receptores Depuradores/fisiologia
16.
Sci Rep ; 7(1): 13771, 2017 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-29062118

RESUMO

Propensity score matching evaluates the treatment incidence of radiation-induced pneumonitis (RP) and secondary cancer risk (SCR) after intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for breast cancer patients. Of 32 patients treated with IMRT and 58 who received VMAT were propensity matched in a 1:1 ratio. RP and SCR were evaluated as the endpoints of acute and chronic toxicity, respectively. Self-fitted normal tissue complication probability (NTCP) parameter values were used to analyze the risk of RP. SCRs were evaluated using the preferred Schneider's parameterization risk models. The dosimetric parameter of the ipsilateral lung volume receiving 40 Gy (IV40) was selected as the dominant risk factor for the RP NTCP model. The results showed that the risks of RP and NTCP, as well as that of SCR of the ipsilateral lung, were slightly lower than the values in patients treated with VMAT versus IMRT (p ≤ 0.01). However, the organ equivalent dose and excess absolute risk values in the contralateral lung and breast were slightly higher with VMAT than with IMRT (p ≤ 0.05). When compared to IMRT, VMAT is a rational radiotherapy option for breast cancer patients, based on its reduced potential for inducing secondary malignancies and RP complications.


Assuntos
Neoplasias da Mama/radioterapia , Segunda Neoplasia Primária/etiologia , Pontuação de Propensão , Pneumonite por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Prognóstico , Pneumonite por Radiação/etiologia , Dosagem Radioterapêutica , Fatores de Risco , Taiwan/epidemiologia
17.
Onco Targets Ther ; 10: 2069-2075, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28435298

RESUMO

PURPOSE: Cranial nerve (CN) palsy is the main symptom in patients with locally advanced nasopharyngeal carcinoma (NPC). This study aimed to evaluate the therapeutic outcome of NPC with CN palsy and to analyze the prognostic factors. PATIENTS AND METHODS: A total of 104 NPC patients with CN palsy curatively treated by conventional (n=44) or conformal (n=60) radiotherapy (RT) were enrolled. Upper CN palsy was present in 81 patients, lower CN palsy in four patients, and both upper and lower CN palsy in 19 patients. Forty-one patients had CN palsy for >2 months before diagnosis. RESULTS: Complete recovery of CN palsy was observed in 74 patients. The actuarial 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 58.2%, 62.2%, and 38.4%, respectively. No significant difference was observed in CN recovery, LRC, DMFS, or OS for patients treated by conventional versus conformal technique. However, significant reduction of grade 3 or greater toxicities was found in those treated by the conformal technique (odds ratio =0.28). CONCLUSION: Patients with CN palsy presenting >2 months before diagnosis were hard to recover from palsy. The LRC, OS, and recovery from CN palsy did not significantly change with the treatment evolution. Patients with complete recovery from CN palsy had longer OS.

18.
Gynecol Oncol ; 145(2): 277-283, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28274568

RESUMO

PURPOSE: To evaluate the differences in the treatment outcomes and complications between elderly patients and younger patients with uterine cervical cancer (CxCa). METHODS AND MATERIALS: From April 1993 to December 2007, 138 CxCa patients aged ≥75years (Elderly group) and 334 CxCa patients aged <60years (Young group) who underwent definitive radiotherapy/chemoradiotherapy at our institution were reviewed. Two propensity score-matched cohorts of patients were selected from both age groups to evaluate the differences in the outcomes and complications. The overall survival (OS), cancer-specific survival (CSS), local failure (LF), distant failure (DF), late proctitis, and cystitis were compared between the age groups. RESULTS: The median follow-up time for survivors was 60.6months. A cohort of 99 pairs of patients was selected for the outcome comparison; there was a significant difference in the 5-year OS between the Elderly and Young groups (49.2% and 71.5%, respectively; p<0.001) but no differences in CSS, LF, and DF. Another cohort of 79 pairs of patients was selected for complication analysis. Significant differences between the Elderly and Young groups were observed in the 5-year cumulative grade 2 proctitis (39.7% and 17.2%, respectively; p=0.015) and grade 3 proctitis (18.1% and 6.2%, respectively; p=0.040). CONCLUSIONS: Although OS was worse in the elderly patients, no differences were observed in CSS, LF, and DF. Meanwhile, elderly patients tended to have higher radiation-related proctitis than younger patients. A more conservative treatment strategy for elderly CxCa patients is reasonable in our future practice.


Assuntos
Neoplasias do Colo do Útero/radioterapia , Fatores Etários , Idoso , Braquiterapia/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Radioterapia/efeitos adversos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
19.
PLoS One ; 10(8): e0132426, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26274393

RESUMO

BACKGROUND: Reactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 20-50% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences. AIM: To investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis. METHODS: A retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies. RESULTS: A total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] vs 4.3% [6/140]); P = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% vs 4.1%, P = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively. CONCLUSION: Severe acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and rituximab-based chemotherapy are the risk factors related to severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients undergoing chemotherapy.


Assuntos
Hepatite B/tratamento farmacológico , Hepatite B/patologia , Alanina Transaminase/sangue , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/tratamento farmacológico , Hepatite B/sangue , Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico
20.
Hepatology ; 62(2): 387-96, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26041578

RESUMO

UNLABELLED: Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry-based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry-based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P < 0.001), whereas the adequate HBV prophylactic rates in the two order entry-based stages were comparable (41.1% versus 39.2%). Patients in the order entry-based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P < 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P < 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P < 0.01). CONCLUSION: A computerized order entry-based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Endêmicas , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/prevenção & controle , Neoplasias/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , Doença Aguda , Adulto , Idoso , Análise de Variância , Anticorpos Monoclonais Murinos/administração & dosagem , Antivirais/uso terapêutico , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/patologia , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Rituximab , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
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