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1.
World J Urol ; 41(12): 3867-3876, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37823940

RESUMO

PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.


Assuntos
Imagem por Ressonância Magnética Intervencionista , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Curva de Aprendizado , Anestesia Local , Estudos Prospectivos , Imagem por Ressonância Magnética Intervencionista/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Dor
2.
Eur Radiol ; 32(9): 6545-6553, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35357538

RESUMO

OBJECTIVE: To evaluate the efficacy of parameters derived from [68Ga]Ga-PSMA-11 PET/CT images in predicting pathological HIF-2α expression in primary tumors among patients with renal cell carcinoma (RCC). METHODS: Fifty-three RCC patients with preoperative [68Ga]Ga-PSMA-11 PET/CT scans and complete surgical specimens were retrospectively enrolled in this study. Radiographic parameters were obtained from PET/CT images, and immunohistochemistry was used to measure the expression of HIF-2α and PSMA. Continuous variables and categorical variables were analyzed by the Mann-Whitney U test and chi-square test, respectively. ROC analysis was used to test the efficacy of several preoperative parameters in identifying pathological HIF-2α expression. Univariable logistic regression analyses were performed for significant parameters to predict pathological HIF-2α expression in RCC. RESULTS: Of the 53 tumors, 29 (54.7%) had high expression of HIF-2α. The SUVmax was significantly different in the HIF-2α expression subgroups (p < 0.001). SUVmax emerged as the most significant parameter to differentiate HIF-2α expression subgroups (high vs. low), with the AUC of 0.93 (95% CI 0.85-1.00, p < 0.001), sensitivity of 90%, and specificity of 88%. Furthermore, SUVmax was confirmed as the most significant predictor of HIF-2α expression level by univariable logistic regression model analysis (odds ratio 1.39, 95% CI 1.17-1.65, p < 0.001). Consistent with the radiographic results of [68Ga]Ga-PSMA-11 PET/CT, the staining intensity of pathological PSMA was significantly higher in HIF-2α-high-expressing tumors (p = 0.003). CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT was superior in identifying pathological HIF-2α expression in primary tumors of RCC patients, demonstrating its potential application in predicting responses to HIF-2α antagonists. KEY POINTS: • [68Ga]Ga-PSMA-11 PET/CT could potentially predict the HIF-2α expression of primary tumors among patients with RCC. • SUVmaxof [68Ga]Ga-PSMA-11 PET/CT was the most significant predictor of HIF-2α expression level. • This probability could help predict the therapeutic response of patients with RCC to HIF-2α antagonists.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Ácido Edético , Radioisótopos de Gálio , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos
3.
Zhonghua Nan Ke Xue ; 28(11): 1006-1010, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-37846116

RESUMO

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5-34.9) kg/m2 , median prostate volume of 132.4 (85.6-235.7) ml, and preoperative tPSA of 10.8 (0.5-37.9) ng/ml, IPSS of 25 (3-35) and quality of life (QOL) score of 5 (3-8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100-285) min, intraoperative blood loss of 200 (50-800) ml, hemoglobin decrease of 25 (4-57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2-7) d, and urinary catheterization of 12 (4-18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 [1-7]), Qmax (19.6 [9.9-32.1] ml/s), PVR (0 [0-34.9] ml) and QOL score (2 [0-3]) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 [19-24]) and MSHQ scores (14 [13-14]) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.


Assuntos
Hiperplasia Prostática , Robótica , Ressecção Transuretral da Próstata , Humanos , Masculino , Idoso , Próstata/cirurgia , Próstata/patologia , Qualidade de Vida , Hiperplasia Prostática/patologia , Robótica/métodos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Hiperplasia/complicações , Hiperplasia/patologia , Ressecção Transuretral da Próstata/métodos , Hemoglobinas , Resultado do Tratamento , Prostatectomia/métodos
5.
Urol Oncol ; 39(10): 734.e19-734.e24, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256990

RESUMO

PURPOSE: This study is to evaluate the safety and feasibility of local anesthesia (LA) for percutaneous ultrasound/computed tomography (US/CT)-guided bipolar radiofrequency ablation (RFA) for small renal masses (SRMs) by comparing the LA with general anesthesia. MATERIALS AND METHODS: A retrospective review was carried out between January 2018 to June 2020, 102 patients with SRMs were treated with US/CT-guided bipolar RFA. General anesthesia (GA) was performed in 42 and LA was performed in 60 patients. Demographics, tumor characteristics, peri-procedural data, pathologic and follow-up outcomes were analyzed. The factors associated with pain were also identified. RESULTS: There was no significant difference in demographics and tumor characteristics between the LA and GA group. A statistically significant difference was observed in terms of procedural time (P = 0.010) and hospital stays (P < 0.001). The maximum perceived pain in LA group comprised 60.0% (36 of 60) mild, 40.0% (24 of 60) moderate. The anxiety in LA group comprised 65.0% (39 of 60) mild, 33.3% (20 of 60) moderate, 1.7% (1 of 60) severe. On multivariate analysis, tumor diameter was a significant predictor for pain in RFA procedure (OR 1.560, 95% CI 1.233-1.974, P < 0.001). All patients were followed up for a median (range) of 12 (2-24) months. Local recurrence occurred in 8.3% (5 of 60) of the LA group and in 7.1% (3 of 42) in GA group (P = 1.000). CONCLUSION: Percutaneous bipolar RFA of SRMs using CT and ultrasound guidance under LA can be an effective and tolerable method for patients who are unfit for surgery and provide satisfactory oncologic control.


Assuntos
Anestesia Local/métodos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/radioterapia , Ablação por Radiofrequência/métodos , Ultrassonografia/métodos , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
6.
BJU Int ; 127(1): 122-130, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32455504

RESUMO

OBJECTIVE: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia. PATIENTS AND METHODS: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP). RESULTS: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall. CONCLUSIONS: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP.


Assuntos
Anestesia Local , Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Biópsia com Agulha de Grande Calibre/efeitos adversos , Hematúria/etiologia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Dor Pós-Operatória/etiologia , Ereção Peniana , Períneo , Estudos Prospectivos , Micção
7.
J Urol ; 205(4): 1082-1089, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33207140

RESUMO

PURPOSE: We explored the role of 68Ga-PSMA-11 positron emission/computerized tomography as a predictor of pathological response to neoadjuvant androgen deprivation therapy combined with abiraterone for high risk prostate cancer. MATERIALS AND METHODS: A total of 45 patients with localized high risk prostate cancer who had serial 68Ga-PSMA-11 positron emission tomography/computerized tomography scans before and after 6 months of androgen deprivation therapy plus abiraterone neoadjuvant treatment followed by radical prostatectomy were included in this study. Complete pathological response or minimal residual disease <5 mm on whole mount histopathology was defined as favorable pathological response. The diagnostic performance of prostate specific antigen response and positron emission tomography/computerized tomography response for favorable pathological response was calculated. Univariable and multivariable logistic regression analyses of clinical and imaging variables were also performed to identify favorable pathological response. RESULTS: Compared to the prostate specific antigen response, positron emission tomography/computerized tomography response had a significantly higher specificity in diagnosing favorable pathological response (89.7% vs 62.1%, p=0.043). Preoperative nadir prostate specific antigen (OR 0.121, 95% CI 0.028-0.529, p=0.005), posttreatment maximum standardized uptake value (OR 7.072, 95% CI 2.035-24.579, p=0.002) and posttreatment tumor volume (OR 7.896, 95% CI 1.415-44.054, p=0.018) measured on positron emission tomography/computerized tomography were significantly associated with favorable pathological response in univariable logistic regression analysis. On multivariable logistic regression analysis, only posttreatment maximum standardized uptake value was found to be an independent predictor of favorable pathological response (OR 9.69, 95% CI 1.439-65.242, p=0.020). CONCLUSIONS: 68Ga-PSMA positron emission tomography/computerized tomography has a better diagnostic performance of pathological response to neoadjuvant treatment compared with prostate specific antigen, with maximum standardized uptake value being an independent predictive factor. This pilot study suggests that prostate specific membrane antigen positron emission tomography/computerized tomography may serve as a potential predictor of pathological response to neoadjuvant treatment.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Biomarcadores Tumorais/sangue , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Oligopeptídeos , Projetos Piloto , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia
8.
J Nanobiotechnology ; 18(1): 124, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887622

RESUMO

BACKGROUND: Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. METHODS: The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. RESULTS: The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. CONCLUSION: A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Musculares/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Polímeros/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Terapia Combinada , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Tratamento Farmacológico/métodos , Humanos , Raios Infravermelhos , Terapia a Laser , Lasers , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Musculares/patologia , Neoplasias Musculares/radioterapia , Músculos/efeitos dos fármacos , Fototerapia/métodos , Polietilenoglicóis , Sensibilidade e Especificidade , Succinimidas , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/radioterapia
9.
J Urol ; 204(6): 1209-1215, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32628099

RESUMO

PURPOSE: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain. MATERIALS AND METHODS: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection. RESULTS: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain. CONCLUSIONS: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.


Assuntos
Anestesia Local , Ansiedade/epidemiologia , Dor Processual/epidemiologia , Neoplasias da Próstata/diagnóstico , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/psicologia , Biópsia com Agulha de Grande Calibre/efeitos adversos , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/psicologia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/psicologia , Imagem por Ressonância Magnética Intervencionista , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Imageamento por Ressonância Magnética Multiparamétrica , Medição da Dor , Dor Processual/diagnóstico , Dor Processual/etiologia , Dor Processual/prevenção & controle , Períneo/cirurgia , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Medição de Risco/métodos , Fatores de Risco , Ultrassonografia de Intervenção
10.
Artif Cells Nanomed Biotechnol ; 46(sup2): 356-363, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607699

RESUMO

Cisplatin is widely used in cancer treatment, but the application is limited due to toxicities and its acquired resistance. In this study, we delivered cisplatin to prostate cancer cells by linking the platinum prodrug Pt(IV) to melanin-like nanoparticles (MeNPs), a promising photothermal therapeutic agent with excellent biocompatibility. As expected, the Pt(IV)-MeNPs exhibited brilliant synergic photothermal-chemotherapy upon near-infrared reflection exposure. Compared with free cisplatin, Pt(IV)-MeNPs displayed highly effective antitumour activity both in vitro and in vivo.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Portadores de Fármacos/química , Melaninas/química , Nanopartículas/química , Fototerapia , Pró-Fármacos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/metabolismo , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Células PC-3
11.
Int J Nanomedicine ; 12: 7777-7787, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29123392

RESUMO

Resistance to regular treatment strategies is a big challenge in the treatment of castration-resistant prostate cancer. Combination of photothermal and photodynamic therapy (PTT/PDT) with chemotherapy offers unique advantages over monotherapy alone. However, free drugs, such as photosensitizers and chemotherapeutic agents, lack tumor-targeted accumulation and can be easily eliminated from the body. Moreover, most of the PTT drugs are hydrophobic and their organic solvents have in vivo toxicity, thereby limiting their potential in clinical translation. Herein, simple multifunctional nanoparticles (NPs) using IR780 (a near-infrared dye) and docetaxel (DTX)-loaded nanoplatform based on human serum albumin (HSA) (HSA@IR780@DTX) was developed for targeted imaging and for PTT/PDT with chemotherapy for the treatment of castration-resistant prostate cancer treatment. In this platform, HSA is a biocompatible nanocarrier that binds to both DTX and IR780. DTX and IR780, as hydrophobic drug, can induce the self-assembly of HSA proteins. Transmission electron microscopic imaging showed that NPs formed by self-assembly are spherical with a smooth surface with a hydrodynamic diameter of 146.5±10.8 nm. The cytotoxicity of HSA@IR780@DTX NPs with or without laser irradiation in prostate cancer cells (22RV1) was determined via CCK-8 assay. The antitumor effect of HSA@IR780@DTX plus laser irradiation was better than either HSA@IR780@DTX without laser exposure or single PTT heating induced by HSA@IR780 NPs under near-infrared laser, suggesting a significant combined effect in comparison to monotherapy. Near-infrared fluorescence imaging showed that HSA@IR780@DTX NPs could preferentially accumulate in tumors. In vivo therapeutic efficacy experiment showed that xenografted prostate tumors on mice treated with HSA@IR780@DTX plus near-infrared laser irradiation were completely inhibited, whereas tumors on mice treated with chemotherapy alone (HSA@DTX and HSA@IR780@DTX without laser) or PTT/PDT alone (HSA@IR780 with laser) showed moderate growth inhibition. Overall, HSA@IR780@DTX NPs showed notable targeting and theranostic potential for the treatment of castration-resistant prostate cancer.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Albuminas/química , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Docetaxel , Humanos , Interações Hidrofóbicas e Hidrofílicas , Indóis/química , Raios Infravermelhos , Masculino , Camundongos Nus , Fotoquimioterapia/métodos , Fototerapia/métodos , Taxoides/química , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Nanomedicine ; 12: 1827-1840, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331308

RESUMO

Dopamine is a neurotransmitter commonly used in clinical treatment. Polydopamine (PDA) has excellent histocompatibility and biosafety and can efficiently convert near-infrared reflection (NIR) to thermal energy. In this study, PDA was used as a promising carrier, and pH-responsive polymer-coated drug-loaded PDA nanoparticles (NPs; doxorubicin@ poly(allylamine)-citraconic anhydride [Dox@PAH-cit]/PDA NPs) were developed. As expected, the Dox@PAH-cit/PDA NPs exhibited excellent photothermal efficiency. In addition, at a low pH condition, the loaded Dox was released from the NPs due to the amide hydrolysis of PAH-cit. Upon NIR exposure (808 nm), the temperature of the NP solution rapidly increases to kill tumor cells. Compared with unbound chemotherapy drugs, the NPs have a stronger cell uptake ability. In vivo, the PDA NPs were able to efficiently accumulate at the tumor location. After intravenous administration and NIR exposure, tumor growth was significantly inhibited. In summary, the present investigation demonstrated that the Dox@PAH-cit/PDA NPs presented highly effective photothermal chemotherapy for prostate cancer.


Assuntos
Materiais Revestidos Biocompatíveis/química , Doxorrubicina/uso terapêutico , Hipertermia Induzida , Indóis/química , Melaninas/química , Nanopartículas/química , Neoplasias/terapia , Fototerapia , Polímeros/química , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Endocitose/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Concentração Inibidora 50 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Poliaminas/química
13.
Mol Pharm ; 13(3): 829-38, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26713719

RESUMO

PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles were intended to accumulate in renal tumor after systemic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaken by RENCA cells mainly through caveola-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting a promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destroy RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulting in only limited injury to normal renal tissue surrounding tumor sites. Our data indicated that PEG-IR780-C13 micelles mediating PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.


Assuntos
Hipertermia Induzida , Indóis/farmacologia , Raios Infravermelhos , Neoplasias Renais/terapia , Fototerapia , Polietilenoglicóis/química , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Citometria de Fluxo , Técnicas Imunoenzimáticas , Neoplasias Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Microscopia Confocal , Espectroscopia de Luz Próxima ao Infravermelho , Células Tumorais Cultivadas
14.
Integr Cancer Ther ; 13(3): 249-58, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24287876

RESUMO

Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in South American medicine. A recent study showed that Pao extract repressed androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao extract asserts its anticancer effects on metastatic castration-resistant prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a dose- and time-dependent manner, through induction of apoptosis and cell cycle arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-xL, and XIAP expression, which were associated with the cleavage of PARP protein. Moreover, Pao extract treatment blocked PC3 cell migration and invasion. Mechanistically, Pao extract suppressed phosphorylation levels of AKT and NFκB/p65, NFκB DNA binding activity, and luciferase reporter activity. Pao inhibited TNFα-induced relocation of NFκB/p65 to the nucleus, NFκB/p65 transcription activity, and MMP9 activity as shown by zymography. Consistently, NFκB/p65 downstream targets involved in proliferation (Cyclin D1), survival (Bcl-2, Bcl-xL, and XIAP), and metastasis (VEGFa, MMP9, and GROα/CXCL1) were also downregulated by Pao extract. Finally, forced expression of NFκB/p65 reversed the growth inhibitory effect of Pao extract. Overall, Pao extract induced cell growth arrest, apoptosis, partially through inhibiting NFκB activation in prostate cancer cells. These data suggest that Pao extract may be beneficial for protection against CRPC.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Invasividade Neoplásica/prevenção & controle , Extratos Vegetais/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/patologia , Transdução de Sinais/efeitos dos fármacos , América do Sul , Fatores de Tempo , Árvores/química
15.
J Ethnopharmacol ; 125(1): 41-6, 2009 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-19560530

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide (TPT), a component of the Chinese herb Triptergium wilfordii, has potent immunosuppressive and anti-inflammatory activity and is used clinically in recipients of kidney transplantation. AIM OF THE STUDY: This work aimed to investigate the effect of TPT on the differentiation of regulatory T lymphocytes (Tregs) from CD4+ cells in rats. MATERIALS AND METHODS: MACS-purified rat CD4+ cells were costimulated with anti-CD3 and anti-CD28 in the presence of TGF-beta to induce the expression of FoxP3, which was detected by flow cytometry. TPT and cyclosporine A (CsA) were separately added into the cultures to observe the effect on the expression of FoxP3. Kidney transplantation was performed in rats that either received no treatment or were treated with TPT after transplantation. RESULTS: TPT treatment enhanced the expression of FoxP3 in CD4+ cells, whereas CsA inhibited the FoxP3 expression. In the rat kidney transplantation model, the recipient rats treated with TPT survived longer than the control rats (18-19.83 vs 6.83 days, P<0.05). Meanwhile, the FoxP3+ T cells in the spleens of treated rats were higher than those from the untreated rats (12.4% vs 4.7%, P<0.05). CONCLUSIONS: These data suggest that TPT may promote the differentiation of CD4+ cells to FoxP3+ Tregs. This would be at least one of the pathways responsible for the immunosuppressive activity of TPT.


Assuntos
Diterpenos/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Imunossupressores/farmacologia , Fenantrenos/farmacologia , Linfócitos T Reguladores/metabolismo , Animais , Antígenos CD4/imunologia , Diferenciação Celular/efeitos dos fármacos , Compostos de Epóxi/farmacologia , Citometria de Fluxo , Transplante de Rim , Ratos , Ratos Endogâmicos Lew , Baço/efeitos dos fármacos , Baço/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Regulação para Cima
16.
Zhonghua Nan Ke Xue ; 11(6): 431-2, 437, 2005 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15999487

RESUMO

OBJECTIVE: To analyze and reduce the omission factors in detecting early stage prostate cancer by TRUS needle biopsy, and to improve the diagnosis of the disease. METHODS: A total of 80 benign prostatic hyperplasia patients suspected of prostatic carcinoma underwent TRUS sextant biopsies. The pathological results being negative, the patients received transurethral resection of the prostate (TURP). RESULTS: After TURP, 25 cases were pathologically diagnosed as prostate cancer, with an omission rate of 31.25% (25/80). Of the diagnosed cancer patients, 10 were treated by radical perineum prostatectomy, 8 by surgical castration, and 7 by medical castration. CONCLUSION: Some tumors may fail to be detected by TRUS needle biopsy. Serial or multi-core needle biopsies can decrease the omission rate in the diagnosis of organ confined cancer.


Assuntos
Próstata/patologia , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/métodos , Erros de Diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Reto/diagnóstico por imagem , Ressecção Transuretral da Próstata , Ultrassonografia de Intervenção
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