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  • 1
    Electronic Resource
    Electronic Resource
    Effects of131I-labeled TNT-1 radioimmunotherapy on HT-29 human colon adenocarcinoma spheroids (1991)
    Springer
    Cancer immunology immunotherapy 33 (1991), S. 158-164 
    Details
    ISSN: 1432-0851
    Keywords: Tumor spheroid ; Tumor necrosis treatment ; Radioimmunotherapy ; Human colon adenocarcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Radiolabeled murine monoclonal antibody TNT-1, directed against the nuclear histones of degenerating cells, was used to treat human colon adenocarcinoma HT-29 spheroids in vitro. The therapeutic effects of131I-TNT-1 were investigated as a function of the radioactive dose, treatment time, and number of treatments. Efficacy of treatment was assessed by TNT-1 antibody uptake, spheroid growth delay, and morphological examination using light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). From these studies, it was determined that the therapeutic effect increased with the number of doses and the duration of treatment. Spheroids treated for 24 h showed approximately two to four times more cell death than those with a 2-h treatment. As previously shown in animal models, additonal treatment with radiolabeled TNT-1 produced an expanding number of TNT-1 targets, and subsequent treatments were more effective as shown by antibody uptake studies. Microscopic examinations demonstrated that morphological changes consistent with spheroid destruction correlated well with antibody uptake data and increased gradually with dose, treatment time, and frequency of treatments. At the ultrastructural level, destruction of cells in the treated spheroids included the formation of porous cell membranes, crater-like holes (SEM), blebbing, and dissolution of cytoplasmic organelles (TEM). With continued culture, the injured spheroids were found to disaggregate after intensive131I-TNT-1 therapy (e.g. 50 µCi/ml or 100 µCi/ml with two or three 24-h treatments). These findings suggest that tumor spheroids can be used as an in vitro model to evaluate monoclonal antibody therapy using TNT-1 and other candidate mAbs directed against intracellular antigens exposed in degenerating cells of tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01756136
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    Paper (German National Licenses)
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  • 2
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    miR-144-3p exerts anti-tumor effects in glioblastoma by targeting c-Met (2015)
    Wiley-Blackwell
    Details
    Publication Date: 2015-08-09
    Description: The paper aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma (GBM) cells with different PTEN (Phosphatase and Tensin homolog) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3′ UTR and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over-expression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide (TMZ) sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy by targeting MET and then inhibiting downstream signaling. This article is protected by copyright. All rights reserved.
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The International Society for Neurochemistry.
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  • 3
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    IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients (2018)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2018-02-02
    Description: Host immunity influences the impact of radiotherapy (RT) in cancer, but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non–small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during, and after RT administration and then correlated to overall survival (OS), progression-free survival, and disease progression rate in patients. We found the impact of RT on these serum IDO markers to be heterogeneous in patients. On average, kynurenine:tryptophan ratios were reduced during RT but restored after RT. Notably, both baseline levels of kynurenine:tryptophan and changes in the levels of kynurenine after RT were significantly associated with OS. When combined, favorable change and favorable baseline corresponded with very long-term OS (median OS was not reached after 57 months of median follow-up). Favorable change combined with unfavorable baseline still corresponded with a lack of distant metastases. Our results suggest that RT alters IDO-mediated immune status in NSCLC patients and that changes in this serum biomarker may be useful to predict outcomes and perhaps personalize RT dosage to improve survival.Significance: Radiotherapy appears to influence systemic IDO activity and to exert a significant impact on metastatic risk and overall survival, with possible implications for defining a biomarker to optimize radiation dose in patients to improve outcomes. Cancer Res; 78(3); 809–16. ©2017 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 4
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    Targeting Histone deacetylase 4/Ubc9 impairs DNA repair for radiosensitization of hepatocellular carcinoma cells (2017)
    Wiley-Blackwell
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    Publication Date: 2017-06-25
    Description: Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2.5-10 Gy). We evaluated cell survival by a clonogenic assay; apoptosis by annexin-V immunofluorescence; γH2AX, Rad51, and HDAC4 by immunofluorescence staining; HDAC4, Rad51, and Ubc9 in HCC cell nuclei by cell fractionation and confocal microscopy; physical interaction between HDAC4/Rad51/Ubc9 by immunoprecipitation; the downstream targets of HDAC4 knockdown by immunoblotting. Both HDAC4 knockdown and HDAC inhibitor enhanced radiation-induced cell death, and reduced homologous recombination repair of DNA double-strand breaks and Akt activation, leading to increased apoptosis. HDAC4 knockdown with or without an HDAC inhibitor significantly delayed tumor growth in a radiation-treated xenograft model. Radiation stimulated nuclear translocation of Rad51 in an HDAC4-dependent manner and the binding of Ubc9 directly to HDAC4, which led to Ubc9 acetylation. Moreover, these effects were accompanied by HDAC4/Ubc9/Rad51 complex dissociation through inhibiting nuclear translocation. Conclusions : HDAC4 signaling blockade enhances radiation-induced lethality in HCC cells and xenografts. These findings raise the possibility that HDAC4/Ubc9/Rad51 complex in DNA repair may be a target for radiosensitization of HCC. This article is protected by copyright. All rights reserved.
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The American Association for the Study of Liver Diseases.
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  • 5
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    IJERPH, Vol. 13, Pages 678: Sugar-Sweetened Beverage Consumption Is Adversely Associated with Childhood Attention Deficit/Hyperactivity Disorder (2016)
    MDPI Publishing
    Details
    Publication Date: 2016-07-05
    Description: Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar-sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers’ characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend 〈 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted.
    Print ISSN: 1661-7827
    Electronic ISSN: 1660-4601
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by MDPI Publishing
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  • 6
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    1.0T MR-guided percutaneous coaxial cutting needle biopsy in pancreatic lesion diagnosis (2018)
    Wiley-Blackwell
    Details
    Publication Date: 2018-01-11
    Description: Background Pancreatic carcinoma is a common cause of cancer deaths worldwide. Biopsy is often required for the initial diagnosis of pancreatic masses. Biopsy can be performed endoscopically or percutaneously with computed tomography (CT) and ultrasound (US) guidance. MRI offers many inherent advantages over CT and US. Purpose/Hypothesis To prospectively evaluate the feasibility, accuracy, and safety of MRI-guided percutaneous coaxial cutting needle biopsy of pancreatic lesions using an open 1.0T high-field MR scanner. Study Type Prospective. Population Thirty-one patients with 31 pancreatic lesions underwent MR-guided percutaneous coaxial cutting needle biopsy. Field Strength/Sequence 1.0T T 2 WI-TSE PDW-aTSE T 1 WI-TFE. Assessment Final diagnosis was confirmed by surgery and clinical follow-up for at least 12 months. The accuracy, sensitivity, and specificity were calculated. Complications were recorded. Statistical Tests There was no statistical analysis in this study. Results The procedure was technically successful and final biopsy samples were adequate for histopathological examination in all patients. Biopsy pathology revealed malignant pancreatic tumor in 25 patients (25/31, 80.6%), and benign pancreatic lesions were present in six patients (6/31, 19.4%). The final diagnosis was pancreatic malignancy in 27 patients and benign disease in four patients, which was confirmed by surgery and clinical follow-up. Two biopsy results were false-negative. The diagnostic accuracy in biopsies was 93.5% (29 of 31). The sensitivity to detect a malignant disease was 92.6% (25 of 27), and the specificity was 100%. All patients tolerated the procedure well; minor peripancreatic hemorrhage was found in two patients after the procedure, and none had major complications either during or after the procedure. Data Conclusion MRI-guided percutaneous biopsy of pancreatic lesions using an open 1.0T high-field scanner has high diagnostic accuracy, which is feasible and safe for use in clinical practice. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 7
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    Activation of invariant natural killer T cells impedes liver regeneration via both IFN-γ- and IL-4-dependent mechanisms (2014)
    Wiley-Blackwell
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    Publication Date: 2014-03-14
    Description: Invariant natural killer T (iNKT) cells are a major subset of lymphocytes found in the liver. These cells mediate various functions, including hepatic injury, fibrogenesis, and carcinogenesis. However, the function of iNKT cells in liver regeneration remains unclear. In the present study, partial hepatectomy (PHx) was used to study liver regeneration. α-GalCer, a specific ligand for iNKT cells, was used to induce iNKT cell activation. After PHx, two strains of iNKT cell-deficient mice, CD1d -/- and Jα281 -/- mice, showed normal liver regeneration. Injection of α-GalCer before or after PHx, which rapidly stimulated IFN-γ and IL-4 production by iNKT cells, markedly inhibited liver regeneration. In vitro treatment with IFN-γ inhibited hepatocyte proliferation. In agreement with this in vitro finding, genetic disruption of IFN-γ or its downstream signaling molecule signal transducer and activator of transcription (STAT)1 significantly abolished the α-GalCer-mediated inhibition of liver regeneration. In vitro exposure to IL-4 did not affect hepatocyte proliferation, but surprisingly, genetic ablation of IL-4 or its downstream signaling molecule STAT6 partially eliminated the inhibitory effect of α-GalCer on liver regeneration. Further studies revealed that IL-4 contributed to α-GalCer-induced iNKT cell expansion and IFN-γ production, and thereby inhibiting liver regeneration. Conclusions : iNKT cells play a minor role in controlling liver regeneration after PHx under healthy conditions. Activation of iNKT cells by α-GalCer induces the production of IFN-γ, which directly inhibits liver regeneration, and IL-4, which indirectly attenuates liver regeneration by stimulating iNKT cell expansion and IFN-γ production. (H epatology 2014;)
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The American Association for the Study of Liver Diseases.
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  • 8
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    Benign prostatic hyperplasia after prostatic arterial embolization in a canine model: A 3T multiparametric MRI and whole-mount step-section pathology correlated longitudinal study (2017)
    Wiley-Blackwell
    Details
    Publication Date: 2017-02-10
    Description: Purpose To explore the morphological and functional characteristics of prostatic arterial embolization (PAE) in a canine model of benign prostatic hyperplasia (BPH) with 3T multiparametric magnetic resonance imaging (mp-MRI) and whole-mount step-section pathology correlation. Materials and Methods Eight adult male beagle dogs with hormone-induced BPH underwent 3T mp-MRI before and 1, 3, and 6 months after PAE, with subsequent whole-mount step-section pathologic assessment. Images were acquired using T 1 -weighted images ( T 1 WI), T 2 WI, 3D-SPACE, diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), T 2 -mapping, and dynamic contrast-enhanced (DCE) sequences. Variance analysis was performed to assess statistical differences in prostatic volume (PV), apparent diffusion coefficient (ADC), and T 2 values. Pearson correlation analysis was performed to correlate ADC, T 2 , and PV. Results The PV decreased from baseline to 1, 3, and 6 months after PAE from (25.88 ± 7.09) cm 3 to (6.48 ± 2.08) cm 3 , (6.48 ± 3.39) cm 3 , (6.20 ± 2.88) cm 3 . The ADC values sequentially decreased from baseline to 1, 3, and 6 months after PAE from (1497.06 ± 222.72) × 10 −6 mm 2 /s to (1056.00 ± 189.46) × 10 −6 mm 2 /s, (950.48 ± 77.85) × 10 −6 mm 2 /s, (980.98 ± 107.78) × 10 −6 mm 2 /s. The T 2 values decreased from baseline to 1, 3, and 6 months after PAE were (83.74 ± 5.29) msec, (68.72 ± 5.66) msec, (53.96 ± 15.04) msec, (49.81 ± 13.34) msec, respectively. ADC and T 2 values were positively correlated with PV ( r  = 0.823 and 0.744, respectively). Microhemorrhages and hemosiderin were found on SWI after PAE. Conclusion 3T mp-MRI may facilitate noninvasive assessment of morphological and functional changes of BPH after PAE. Level of Evidence: 1 J. Magn. Reson. Imaging 2017
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 9
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    Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients (2017)
    Wiley-Blackwell
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    Publication Date: 2017-05-09
    Description: Purpose To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). Materials and Methods We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, K trans , k ep , v e , v p , and iAUC 60 . Chest computed tomography (CT) was performed at 3 months after SBRT. Results SBRT treatment led to tumor changes including significant decreases in the SUV max (–61%, P 〈 0.001), K trans mean (–72%, P = 0.005), K trans standard deviation (SD; –85%, P = 0.046), k ep mean (–53%, P = 0.014), k ep SD (–63%, P = 0.001), and v p SD (–58%, P = 0.002). The PET SUV max was correlated with the MR k ep mean ( P = 0.002) and k ep SD ( P 〈 0.001). The percentage reduction in K trans mean ( P 〈 0.001) and k ep mean ( P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUV max 〉 10 ( P = 0.083). Conclusion In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. Level of Evidence : 2 Technical Efficacy : Stage 1 J. Magn. Reson. Imaging 2017.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
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  • 10
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    LRF inhibits p53 expression in colon cancer cells via modulating DAP5 activity (2017)
    Wiley-Blackwell
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    Publication Date: 2017-08-30
    Description: The p53 protein plays a critical role in suppression of tumour growth; its regulation is not fully understood. Leukaemia/lymphoma-related factor (LRF) promotes tumour cell growth. This study tests a hypothesis that LRF inhibits p53 expression in colon cancer cells. In this study, human colon cancer cell lines, LIM1215 and HCT116 cells, were used. The expression of LRF and p53 in the cells was analysed by quantitative reverse transcription polymerase chain reaction and Western blotting. We observed that the expression of protease-activated receptor 2 (PAR2) was detected in both LIM1215 and HCT116 human colon cancer cells. Activation of PAR2 increased the expression of LRF and inhibited the p53 expression in the cancer cells. We also detected a complex of LRF and DAP5, one of the p53 gene transcription factors. The interaction of LRF and DAP5 resulted in the repression of p53 expression in the colon cancer cells. In conclusion, PAR2 activation increases the expression of LRF in colon cancer cells, which interacts with DAP5 to repress the p53 expression. Leukaemia/lymphoma-related factor may be a novel target in the treatment of colon cancer.
    Print ISSN: 0263-6484
    Electronic ISSN: 1099-0844
    Topics: Biology , Medicine
    Published by Wiley-Blackwell
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