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To ensure maximum therapeutic safety and efficacy of stem cell transplantation, it is essential to observe the kinetics of behavior, accumulation, and engraftment of transplanted stem cells in vivo. However, it is difficult to detect transplanted stem cells with high sensitivity by conventional in vivo imaging technologies. To diagnose the kinetics of transplanted stem cells, we prepared multifunctional nanoparticles, Gd2O3 co-doped with Er3+ and Yb3+ (Gd2O3: Er, Yb-NPs), and developed an in vivo double modal imaging technique with near-infrared-II (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI) of stem cells using Gd2O3: Er, Yb-NPs. Gd2O3: Er, Yb-NPs were transduced into adipose tissue-derived stem cells (ASCs) through a simple incubation process without cytotoxicity under certain concentrations of Gd2O3: Er, Yb-NPs and were found not to affect the morphology of ASCs. ASCs labeled with Gd2O3: Er, Yb-NPs were transplanted subcutaneously onto the backs of mice, and successfully imaged with good contrast using an in vivo NIR-II fluorescence imaging and MRI system. These data suggest that Gd2O3: Er, Yb-NPs may be useful for in vivo double modal imaging with NIR-II fluorescence imaging and MRI of transplanted stem cells.
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Gadolínio , Imageamento por Ressonância Magnética , Células-Tronco , Gadolínio/química , Animais , Camundongos , Células-Tronco/citologia , Raios Infravermelhos , Transplante de Células-Tronco , Nanopartículas/química , Imagem Óptica , Elementos da Série dos Lantanídeos/química , Tecido Adiposo/citologiaRESUMO
PURPOSE: This study was performed to investigate the effectiveness of hydrodissection during computed tomography-guided renal cryoablation by evaluation of the fluid distribution based on the retroperitoneal anatomy with the interfascial plane. MATERIALS AND METHODS: Between March 2014 and March 2021, 52 renal tumors were treated by cryoablation with hydrodissection (36 men; mean age 72.5 years). The hydrodissection needle was located in perirenal space. The spreading fluid space based on the retroperitoneal anatomy with the interfascial plane was retrospectively evaluated. The fluid space that most effectively separated the tumor from the adjacent organs was defined. The relationship of the needle tip position in the perirenal space (renal capsule or fascia side) and the most effective fluid space was also evaluated. RESULTS: Cryoablation was successfully completed in all cases with no major complications. Hydrodissection was effective in all cases. The distance between the tumors and the adjacent organs was significantly longer after hydrodissection (from 7.50 ± 7.43 to 22.6 ± 9.86 mm) (P < 0.0001). Although fluid spreading through multiple retroperitoneal spaces was frequently observed, the retromesenteric plane was observed more frequently as the most effective fluid space (67.3%) than the perirenal space (21.2%) (P < 0.0001). Regardless of the needle tip position, the most effective fluid space was also commonly the retromesenteric plane. CONCLUSIONS: The retromesenteric plane could be the most effective fluid space to separate the tumor from the adjacent organ, regardless of where the hydrodissection needle tip is positioned in the perirenal space. LEVEL OF EVIDENCE: 3b.
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Criocirurgia , Neoplasias Renais , Masculino , Humanos , Idoso , Espaço Retroperitoneal/cirurgia , Espaço Retroperitoneal/patologia , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Tomografia Computadorizada por Raios XRESUMO
A 72-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) was treated with dasatinib (week1: 50 mg/day, week2: 70 mg/day, week3-: 100 mg/day) and prednisolone from June 2017. However, in January 2018, it relapsed with the T315I mutation. Although the treatment was changed to ponatinib 30 mg/day, he experienced a second relapse in June 2018. Following confirmation of CD22 positivity, he was treated with three cycles of inotuzumab ozogamicin (InO), resulting in CR. He was CR for 2.9 years before relapsing for the third time in May 2021. Because the patient was still CD22-positive, InO was given again, and the patient achieved CR at the end of the second cycle. We had a case where re-administering InO was effective as a salvage therapy for relapsed/refractory Ph+ALL (r/r Ph+ALL) in an elderly patient.
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Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Masculino , Humanos , Inotuzumab Ozogamicina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Retratamento , DasatinibeRESUMO
Peptide-based strategies have received an enormous amount of attention because of their specificity and applicability. Their specificity and tumor-targeting ability are applied to diagnosis and treatment for cancer patients. In this review, we will summarize recent advancements and future perspectives on peptide-based strategies for cancer treatment. The literature search was conducted to identify relevant articles for peptide-based strategies for cancer treatment. It was performed using PubMed for articles in English until June 2023. Information on clinical trials was also obtained from ClinicalTrial.gov. Given that peptide-based strategies have several advantages such as targeted delivery to the diseased area, personalized designs, relatively small sizes, and simple production process, bioactive peptides having anti-cancer activities (anti-cancer peptides or ACPs) have been tested in pre-clinical settings and clinical trials. The capability of peptides for tumor targeting is essentially useful for peptide-drug conjugates (PDCs), diagnosis, and image-guided surgery. Immunomodulation with peptide vaccines has been extensively tested in clinical trials. Despite such advantages, FDA-approved peptide agents for solid cancer are still limited. This review will provide a detailed overview of current approaches, design strategies, routes of administration, and new technological advancements. We will highlight the success and limitations of peptide-based therapies for cancer treatment.
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Neoplasias , Cirurgia Assistida por Computador , Humanos , Neoplasias/tratamento farmacológico , Peptídeos/uso terapêutico , Imunomodulação , PubMedRESUMO
INTRODUCTION: The Glasgow prognostic score (GPS) is an inflammation-related score based on C-reactive protein and albumin concentrations. Few studies have assessed the correlation between the GPS and the efficacy of chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, this study aimed to evaluate the utility of the GPS in predicting the survival outcomes of patients with ES-SCLC. METHODS: This retrospective study evaluated patients with ES-SCLC who had undergone chemotherapy between February 2008 and November 2021. GPS values were evaluated before the initiation of first-line chemotherapy. The Kaplan-Meier method and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: The GPS values of the 113 patients were zero (54 patients, 48%), 1 (37 patients, 33%), and 2 (22 patients, 19%). The median follow-up duration was 10.7 months. Median PFS was 6.2, 5.6, and 3.8 months in the GPS 0, 1, and 2 groups, respectively, suggesting that the GPS zero group had a significantly more favorable PFS than the GPS 2 group (p < 0.001). Median OS was 17.1, 9.4, and 5.6 months in the GPS 0, 1, and 2 groups, respectively, suggesting that the GPS zero group had a significantly more favorable OS than the GPS 2 group (p = 0.001). Multivariate analysis confirmed that a GPS of 2 independently predicted unfavorable PFS (hazard ratio [HR], 2.89; 95% confidence interval [CI]: 1.68-4.88; p < 0.001) and OS (HR, 3.49 [95% CI: 1.83-6.63], p < 0.001). CONCLUSION: The study's findings suggest that the GPS can predict the survival outcomes of patients with ES-SCLC who have undergone chemotherapy. The GPS is an easy-to-calculate biomarker and would be ideal for routine use in clinical settings.
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Vascular endothelial damage may activate hypercoagulation and contribute to the development of acute kidney injury (AKI). This study aimed to investigate whether early alteration in coagulation was associated with AKI onset following surgeries involving cardiopulmonary bypass (CPB) in children. This single-center retrospective cohort study included 154 infants and toddlers who underwent cardiovascular surgery with CPB. At admission to the pediatric intensive care unit, the absolute thrombin-antithrombin complex (TAT) level in each patient was measured. Moreover, the presence or absence of AKI onset in the early postoperative period was observed. Of the total participants, 55 (35%) developed AKI. A comparison within the toddler group based on the TAT cut-off value showed that both univariate and multivariable associations were found between increased absolute TAT level and AKI onset (odds ratio, 4.70; 95% confidence interval [1.20-17.90]; P = .023). The increase in absolute TAT level in toddlers during the early postoperative period following CPB was associated with AKI onset. However, a further prospective multicenter study with a larger sample size is required for validating these findings.
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Injúria Renal Aguda , Ponte Cardiopulmonar , Lactente , Humanos , Criança , Estudos Retrospectivos , Ponte Cardiopulmonar/efeitos adversos , Fatores de Risco , Complicações Pós-Operatórias , Injúria Renal Aguda/etiologiaRESUMO
INTRODUCTION: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. The Glasgow prognostic score (GPS) is an inflammation-assessing score based on C-reactive protein and albumin concentrations. Information regarding the association between the GPS and EGFR-TKI treatment effectiveness is limited; hence, we investigated whether the GPS can predict the response of NSCLC to EGFR-TKIs. METHODS: We evaluated 340 patients with NSCLC harboring sensitive EGFR mutations who received EGFR-TKI monotherapy between March 2009 and July 2021. The Kaplan-Meier method and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: After a median follow-up of 26.6 months, patients with a GPS of 0, 1, and 2 had PFS of 15.7, 10.0, and 6.3 months, respectively, and OS of 40.1, 25.8, and 14.4 months, respectively; patients with a GPS of 0 had significantly better PFS and OS than those with a GPS of 1 (p = 0.03, p = 0.001, respectively) or 2 (p < 0.001, p < 0.001, respectively). Multivariate analysis identified poor performance status, stage 4 at diagnosis, type of EGFR-TKI (gefitinib/erlotinib vs. afatinib), and GPS = 2 as predictors of a short PFS. Meanwhile, poor performance status, gefitinib/erlotinib administration, and GPS = 2 were predictors of a short OS. CONCLUSION: The GPS predicted the survival of NSCLC patients harboring sensitive EGFR mutations who were undergoing EGFR-TKI treatment. The GPS might be ideal for routine use in clinical practice, given that it is an easily calculated parameter.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Gefitinibe/uso terapêutico , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Receptores ErbB/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Malignant hyperthermia is an extremely dangerous condition that can occur with exposure to volatile inhalant anesthetics and depolarizing muscle relaxants, and that requires immediate intervention. Neurological complications have rarely been reported, with no reports of electroencephalographic abnormalities or encephalopathy. Here, we report a case of severe electroencephalographic abnormality in the acute phase of malignant hyperthermia that eventually led to diffuse cerebral cortical damage. CASE PRESENTATION: A 15-month-old Japanese boy underwent a Rastelli procedure to correct a double-outlet right ventricle and pulmonary atresia. Sevoflurane was used for induction and maintenance of anesthesia during surgery. After withdrawal from the heart-lung machine, his body temperature rose at a rate of 0.1 â/minute, and when he left the operating room, his core body temperature had reached 42 â. After admission to the intensive care unit, tachycardia, high PaCO2, and progressive metabolic acidosis were observed. A clinical grading scale score of 63 indicated malignant hyperthermia, and dantrolene was administered. The pupils were dilated, and the electroencephalogram showed persistent generalized continuous multifocal spikes. Midazolam, levetiracetam, and fosphenytoin were administered without improvement, and thiamylal and ketamine were infused continuously. After the electroencephalogram shifted to burst suppression, the epileptic firing gradually decreased, and the background electroencephalogram became lower in amplitude. Magnetic resonance imaging of the head performed after the patient was hemodynamically stable suggested diffuse cerebral cortical damage. Severe mental retardation, hypertonia, and quadriplegia were observed as neurological complications. CONCLUSIONS: In this case, despite the use of high-dose anticonvulsants, the patient showed severe electroencephalogram abnormality, resulting in diffuse cortical damage. Hyperthermia is known to damage the central nervous system by causing increased brain pressure and cerebral edema, which may have triggered the severe neuronal excitation that we observed in this case. The presence of systemic inflammatory response syndrome and the patient's background, including young age and ethnicity, might also have been factors. Malignant hyperthermia can be complicated by encephalopathy, and continuous electroencephalogram monitoring should be considered.
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Lesões Encefálicas , Hipertermia Maligna , Masculino , Humanos , Criança , Lactente , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/etiologia , Dantroleno , Lesões Encefálicas/complicações , Eletroencefalografia/efeitos adversos , EncéfaloRESUMO
Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases.
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Peptídeos Penetradores de Células , Oftalmopatias , Animais , Peptídeos Penetradores de Células/química , Olho/metabolismo , Sistemas de Liberação de Medicamentos , Transporte Biológico , Preparações Farmacêuticas , Oftalmopatias/tratamento farmacológicoRESUMO
Excessive vascular endothelial growth factor-A (VEGF-A) signaling induces vascular leakage and angiogenesis in diseases. VEGFR2 trafficking to the cell surface, mediated by kinesin-3 family protein KIF13B, is essential to respond to VEGF-A when inducing angiogenesis. However, the precise mechanism of how KIF13B regulates VEGF-induced signaling and its effects on endothelial permeability is largely unknown. Here we show that KIF13B-mediated recycling of internalized VEGFR2 through Rab11-positive recycling vesicle regulates endothelial permeability. Phosphorylated VEGFR2 at the cell-cell junction was internalized and associated with KIF13B in Rab5-positive early endosomes. KIF13B mediated VEGFR2 recycling through Rab11-positive recycling vesicle. Inhibition of the function of KIF13B attenuated phosphorylation of VEGFR2 at Y951, SRC at Y416, and VE-cadherin at Y685, which are necessary for endothelial permeability. Failure of VEGFR2 trafficking to the cell surface induced accumulation and degradation of VEGFR2 in lysosomes. Furthermore, in the animal model of the blinding eye disease wet age-related macular degeneration (AMD), inhibition of KIF13B-mediated VEGFR2 trafficking also mitigated vascular leakage. Thus, the present results identify the fundamental role of VEGFR2 recycling to the cell surface in mediating vascular permeability, which suggests a promising strategy for mitigating vascular leakage associated with inflammatory diseases.
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Permeabilidade Capilar , Cinesinas , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Permeabilidade Capilar/genética , Permeabilidade Capilar/fisiologia , Membrana Celular/metabolismo , Cinesinas/metabolismo , Fosforilação , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: To evaluate the time-course changes of multiparametric MRI findings following focal cryotherapy for localized prostate cancer. METHODS: Sixteen patients who underwent focal cryotherapy as an initial curative treatment for localized prostate cancer during March 2017-April 2021 were included. Before the treatment, the patients underwent targeted prostate biopsy using MRI-transrectal ultrasound fusion. Overall, 64 MRIs were conducted after focal cryotherapy and the temporal post-treatment MR signal changes of the ablated area in T2WI, T1WI, DWI, and DCE-MRI were analyzed. RESULTS: Technical success was achieved in all patients. The median follow-up period was 22 months. The initial post-treatment MRI revealed significant signal changes in the target lesions for all patients, including the disappearance of findings suggestive of cancer. At 3 months post-treatment, most lesions were hyperintense with a hypointense rim on T2WI, T1WI, and DWI (83.3 %). After 6 months, hyperintensity reduced, and after 17 months, all lesions showed hypointensity in these sequences. DCE-MRI of most patients showed loss of internal enhancement; however, one patient exhibited residual nodular enhancement in the ablated area at 3 months, which disappeared after 6 months. Peripheral enhancement was common at 3 months, disappearing after 23 months. Two patients showed biopsy-evidenced local recurrence. The recurrent lesions showed hypointensity on T2WI with diffusion restriction and early contrast enhancement in the ventral transition zone. CONCLUSION: MRI findings of the ablated sites following focal cryotherapy for localized prostate cancer show dynamic signal changes, especially within the first 6 months.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico , CrioterapiaRESUMO
INTRODUCTION: Predictors of the effectiveness of immune checkpoint inhibitor (ICI) monotherapy in previously treated patients with non-small cell lung cancer (NSCLC) remain ill-defined. We investigated whether the Glasgow prognostic score (GPS) could serve as such predictors. METHODS: Eighty patients treated with pembrolizumab or atezolizumab monotherapy as second- or subsequent-line therapy for NSCLC were retrospectively reviewed, and the associations between GPS, body mass index (BMI), and each of progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: The median follow-up period was 11.1 months. Patients with a BMI ≥20.4 kg/m2 had significantly longer PFS and OS (3.7 and 22.2 month, respectively) than did those with a BMI <20.4 kg/m2 (2.2 and 11.5 months, respectively). Patients with a GPS of 0 had a significantly longer PFS (6.6 months) than did those with a GPS of 1 (2.2 months, p = 0.002) and 2 (1.8 months, p = 0.029). Patients with a GPS of 0 also had a significantly longer OS (22.2 month) than did those with a GPS of 1 (9.2 months, p = 0.002) and 2 (4.7 months, p = 0.002). Notably, the GPS, BMI, and clinical stage were independent predictors of PFS, while the GPS and performance status were independent predictors of OS. The response rate of patients with a GPS of 0 was significantly higher than that of patients with a GPS of 1-2 (26.2% vs. 7.9%, p = 0.03). CONCLUSION: The GPS is an independent predictor of PFS and OS in patients with NSCLC who received second- or subsequent-line pembrolizumab or atezolizumab monotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Estudos RetrospectivosRESUMO
Lymphangioleiomyomatosis (LAM) is one of the presentations of perivascular epithelioid cell neoplasm that is frequently complicated by tuberous sclerosis complex (TSC). Here, we report an uncommon case of uterine LAM treated with everolimus, which is a mechanistic target of rapamycin (mTOR) inhibitor. A 42-year-old female patient (gravida 0) with a history of TSC presented with abdominal pain. Pelvic magnetic resonance imaging showed multiple masses in the uterine myometrium, suggesting tumors that may contain internal hemorrhagic components. The lesions were suspected as the root cause of her symptoms. After everolimus was administered for a previously diagnosed renal angiolipoma, her uterine tumors temporarily decreased in size. Subsequently, laparoscopic hysterectomy and bilateral salpingectomy were performed since she could not tolerate everolimus for a long period due to the medication's side effects. Furthermore, the patient was diagnosed with LAM through histopathological examination after surgical resection. Therefore, it is advisable to suspect and investigate uterine LAM when a patient with a history of TSC presents with irregular genital bleeding or abdominal pain. Moreover, mTOR inhibitors may be a treatment option, in addition to surgery, in cases of uterine LAM exacerbation.
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The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.
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Nanopartículas de Magnetita , Pontos Quânticos , Animais , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/toxicidade , Camundongos , Imagem Multimodal , Pontos Quânticos/química , Células-TroncoRESUMO
BACKGROUND: We aimed to develop an artificial intelligence (AI) algorithm that predicts the volume and location of clinically significant cancer (CSCa) using convolutional neural network (CNN) trained with integration of multiparametric MR-US image data and MRI-US fusion prostate biopsy (MRI-US PBx) trajectory-proven pathology data. METHODS: Twenty consecutive patients prospectively underwent MRI-US PBx, followed by robot-assisted radical prostatectomy (RARP). The AI algorithm was trained with the integration of MR-US image data with a MRI-US PBx trajectory-proven pathology. The relationship with the 3D-cancer-mapping of RARP specimens was compared between AI system-suggested 3D-CSCa mapping and an experienced radiologist's suggested 3D-CSCa mapping on MRI alone according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2. The characteristics of detected and undetected tumors at AI were compared in 22,968 image data. The relationships between CSCa volumes and volumes predicted by AI as well as the radiologist's reading based on PI-RADS were analyzed. RESULTS: The concordance of the CSCa center with that in RARP specimens was significantly higher in the AI prediction than the radiologist' reading (83% vs. 54%, p = 0.036). CSCa volumes predicted with AI were more accurate (r = 0.90, p < 0.001) than the radiologist's reading. The limitations include that the elastic fusion technology has its own registration error. CONCLUSIONS: We presented a novel pilot AI algorithm for 3D prediction of PCa. AI was trained by integration of multiparametric MR-US image data and fusion biopsy trajectory-proven pathology data. This deep learning AI model may more precisely predict the 3D mapping of CSCa in its volume and center location than a radiologist's reading based on PI-RADS version 2, and has potential in the planning of focal therapy.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata , Inteligência Artificial , Humanos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
VEGF-A induces vascular leakage and angiogenesis via activating the cell surface localized receptor VEGF receptor 2 (VEGFR2). The amount of available VEGFR2 at the cell surface is however tightly regulated by trafficking of VEGFR2 by kinesin family 13 B (KIF13B), a plus-end kinesin motor, to the plasma membrane of endothelial cells (ECs). Competitive inhibition of interaction between VEGFR2 and KIF13B by a peptide kinesin-derived angiogenesis inhibitor (KAI) prevented pathological angiogenesis in models of cancer and eye disease associated with defective angiogenesis. Here, we show the protective effects of KAI in VEGF-A-induced vascular leakage and cancer metastasis. Using an EC-specific KIF13B knockout (Kif13b iECKO ) mouse model, we demonstrated the function of EC expressed KIF13B in mediating VEGF-A-induced vascular leakage, angiogenesis, tumor growth, and cancer metastasis. Thus, KIF13B-mediated trafficking of VEGFR2 to the endothelial surface has an essential role in pathological angiogenesis induced by VEGF-A, and is therefore a potential therapeutic target.
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Permeabilidade Capilar , Cinesinas/metabolismo , Proteínas de Membrana/metabolismo , Metástase Neoplásica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Permeabilidade Capilar/genética , Membrana Celular/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Cinesinas/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Metástase Neoplásica/genética , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Transporte ProteicoRESUMO
INTRODUCTION: Ureteropelvic junction obstruction is a common congenital anomaly that causes hydronephrosis but rarely accompanies ipsilateral retrocaval ureter. CASE PRESENTATION: A 39-year-old woman, who visited to our hospital complaining of worsened right low back pain and fever, was diagnosed with right hydronephrosis due to ureteropelvic junction obstruction by contrast-enhanced computed tomography. Intraoperatively before the planned robot-assisted laparoscopic pyeloplasty, retrograde pyelography was performed to reveal concomitant ipsilateral retrocaval ureter. Laparoscopically, ureteropelvic junction obstruction due to aberrant blood vessel and coexisting retrocaval ureter was confirmed. Transposition of the ureter from posterior to anterior of the inferior vena cava and following dismembered pyeloplasty was performed. Two years after surgery, her right hydronephrosis improved and she had no complain of any symptom. CONCLUSION: Retrocaval ureter is a rare abnormality; however, combination of preoperative retrograde pyelography and laparoscopic evaluation was important for management of this concomitant abnormality.
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Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.
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Histopathological and genetic examinations were conducted on grayish-white solid hepatic nodules in 150 horses imported from Canada, in order to investigate larval Echinococcus multilocularis infection. Ten of the 150 horses (6.7%) were diagnosed with alveolar hydatid disease. The sequences of the mitochondrial cytochrome b genes obtained from all 10 polymerase chain reaction positive samples had 99 to 100% identity with the European haplotype E1 of E. multilocularis. Therefore, we concluded that the infections likely originated in Canada.
Relation entre les nodules hépatiques solides blanc-grisâtre trouvés chez des chevaux importés du Canada et l'infection larvaire à Echinococcus multilocularis . Des examens histopathologiques et génétiques ont été effectués sur des nodules hépatiques solides blanc-grisâtre observés chez 150 chevaux importés du Canada afin d'étudier l'infection larvaire à Echinococcus multilocularis. Dix des 150 chevaux (6,7 %) ont reçu un diagnostic de maladie hydatique alvéolaire. Les séquences des gènes mitochondriaux du cytochrome b obtenus à partir des 10 échantillons positifs par réaction d'amplification en chaîne par la polymérase ont montré une identité de 99 à 100 % avec l'haplotype européen E1 d'E. multilocularis. L'haplotype d'E. multilocularis obtenu à partir de cette étude suggère que les infections sont probablement originaires du Canada.(Traduit par Dr Serge Messier).