Cascade-amplifying synergistic effects of chemo-photodynamic therapy using ROS-responsive polymeric nanocarriers.

The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy. Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as SOHNPCe6/DOX). The therapeutic efficacy of SOHNPCe6/DOX against drug-resistant cancer was evaluated in vitro and in vivo. Results: Under 660-nm light irradiation, SOHNPCe6/DOX can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, SOHNPCe6/DOX also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, SOHNPCe6/DOX realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model. Conclusion: The designed SOHNPCe6/DOX with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.

[Differentiation of axillary inflammatory and metastatic lymph nodes with diffusion-weighted imaging in animal modes].

OBJECTIVE: To evaluate the value of diffusion-weighted imaging (DWI) in the differentiation of axillary inflammatory hyperplastic and metastatic lymph nodes. METHODS: Forty female New Zealand white rabbits were divided randomly into 2 groups (n = 20 each). And the animal models of axillary inflammatory hyperplastic and metastatic lymph nodes were established. All successfully implanted models received conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) examinations. The features of signal intensity and shapes of lymph nodes were observed in two groups. The sizes of lymph nodes were measured on the selected axial T(2)WI. The signal intensity and appearance diffusion coefficient (ADC) value of lymph nodes and dorsal muscle at the same slice were measured on the selected T(2)WI, DWI and ADC map respectively. The relative signal intensity (rSIT(2)WI, rSIDWI) and relative ADC (rADC) value of lymph nodes to dorsal muscle were calculated and compared. The diagnostic efficacy of differentiating benign and malignant lymph nodes was analyzed with rADC value through the receiver operating characteristic curve. The correlation between rADC value and cell density was assessed with pathological findings as reference standard. RESULTS: The differences of size, rSIT(2)WI and rSIDWI were not statistically significant between two groups. The rADC value of inflammatory lymph nodes was greater than that of metastatic lymph nodes (0.91 ± 0.14 vs 0.64 ± 0.18). Significant difference existed (t = 3.879, P = 0.03). But there was a little overlap between two groups. With 0.78 as the diagnostic threshold of rADC value, the sensibility and specificity was 86.2% and 74.4% respectively. The correlation between rADC value and cell density of inflammatory hyperplastic and metastatic lymph nodes was significantly inverse (r = -0.53, P = 0.003). CONCLUSIONS: As compared with the routine MRI sequence, rADC value has a higher diagnostic efficacy in the differentiation of benign and malignant lymph nodes. Cell density may be the most important influencing factor for the differences of rADC value between two groups of lymph nodes.

Magnetic resonance imaging in assessment of treatment response of gamma knife for brain tumors.

OBJECTIVE: To review the applications of magnetic resonance imaging (MRI) techniques in assessing treatment response to gamma knife radiosurgery for brain tumors. DATA SOURCES: Published articles about assessing treatment response to gamma knife radiosurgery for brain tumors were selected using PubMed. The search terms were "MRI", "gamma knife" and "brain tumors". STUDY SELECTION: Articles regarding the MRI techniques using for early assessment of treatment response of gamma knife were selected. RESULTS: MRI techniques, especially diffusion weighted imaging, perfusion weighted imaging, magnetic resonance spectroscopy, are useful for early assessment of treatment response of gamma knife by detecting the hemodynamic, metabolic, and cellular alterations. Moreover, they can also provide important information on prognosis. CONCLUSIONS: Diffusion weighted imaging, perfusion weighted imaging and magnetic resonance spectroscopy can provide early assessment of treatment response of gamma knife for brain tumors, and also information of tumor progression or recurrence earlier than conventional MRI. But there are still many questions to be answered which should be based on the development and advancement of MRI and related disciplines.

Study on HIF-1α Gene Translation in Psoriatic Epidermis with the Topical Treatment of Capsaicin Ointment.

Objective. To investigate the mechanism of capsaicin in treating active psoriasis vulgaris. Methods. HIF-1α gene translation in active psoriatic lesions before and after 21-day treatment with capsaicin ointment was detected by in situ hybridization. Results. There was positive staining of HIF-1α gene in all the layers of psoriatic epidermis (100.0%) before the treatment with capsaicin ointment, but the dyeing in epidermis were reduced obviously (22.2%) after the treatment for 21 days. Conclusion. HIF-1α gene translation in psoriatic epidermis was downregulated after capsaicin treatment for 21 days.

Effects of echo time on diffusion quantification of brain white matter at 1.5 T and 3.0 T.

The aim was to investigate the effects of echo time (TE) on diffusion quantification of brain white matter. Seven rhesus monkeys (all males; age, 4-6 years; weight, 5-7 kg) underwent diffusion tensor imaging (DTI) with a series of TEs in 1.5 T and 3.0 T MR scanners. The mean diffusivity (MD), fractional anisotropy (FA), primary (lambda(1)), and transverse eigenvalues (lambda(23)) were measured in a region of interest at the bilateral internal capsule. Pearson correlation showed that the FA and lambda(1) increased and lambda(23) decreased with TE both at 1.5 T and 3.0 T except for the MD. Repeated measurement analysis of variance (ANOVA) also showed significantly higher FA and lower MD and lambda(23) at 3.0 T than those at 1.5 T (P<0.01), but no statistical differences were found in lambda(1) between these two field strengths (P=0.709). These findings implied that TE and field strength might influence diffusion quantification in brain white matter.

Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis.

OBJECTIVE: The purposes of our study were to employ diffusion tensor imaging (DTI)-based histogram analysis to determine the presence of occult damage in clinically isolated syndrome (CIS), to compare its severity with relapsing-remitting multiple sclerosis (RRMS), and to determine correlations between DTI histogram measures and clinical and MRI indices in these two diseases. MATERIALS AND METHODS: DTI scans were performed in 19 CIS and 19 RRMS patients and 19 matched healthy volunteers. Histogram analyses of mean diffusivity and fractional anisotropy were performed in normal-appearing brain tissue (NABT), normal-appearing white matter (NAWM) and gray matter (NAGM). Correlations were analyzed between these measures and expanded disability status scale (EDSS) scores, T(2)WI lesion volumes (LV) and normalized brain tissue volumes (NBTV) in CIS and RRMS patients. RESULTS: Significant differences were found among CIS, RRMS and control groups in the NBTV and most of the DTI histogram measures of the NABT, NAWM and NAGM. In CIS patients, some DTI histogram measures showed significant correlations with LV and NBTV, but none of them with EDSS. In RRMS patients, however, some DTI histogram measures were significantly correlated with LV, NBTV and EDSS. CONCLUSION: Occult damage occurs in both NAGM and NAWM in CIS, but the severity is milder than that in RRMS. In CIS and RRMS, the occult damage might be related to both T2 lesion load and brain tissue atrophy. Some DTI histogram measures might be useful for assessing the disease progression in RRMS patients.

Silencing livin gene by siRNA leads to apoptosis induction, cell cycle arrest, and proliferation inhibition in malignant melanoma LiBr cells.

AIM: The aim of the present study was to investigate the effects of silencing the livin gene by small interfering RNA (siRNA) on the expression of livin and the effects on apoptosis, cell cycle, and proliferation in human malignant melanoma LiBr cells. METHODS: Three chemically-synthetic siRNA duplexes targeting livin were transiently transfected into the LiBr cells, and the effects on livin expression were detected both at the mRNA level by real-time RT-PCR and at the protein level by Western blotting. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay, flow cytometric analysis, and the expression of procaspase-3 and activated caspase-3 analysis by Western blotting. Cell cycle was analyzed by flow cytometry. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. RESULTS: One of the 3 designed siRNA could effectively knock down the livin expression both at the mRNA and protein levels in dose- and time-dependent manners; 100 nmol/L with maximum downregulation on mRNA at 48 h, and on the protein at 72 h after transfection. Silencing livin could significantly induce apoptosis, arrest cell cycle at the G0/G1 phase, and inhibit proliferation in LiBr cells. Meanwhile, caspase-3 was activated. CONCLUSION: The livin gene could serve as a potential molecular target for gene therapy by siRNA for malignant melanoma.

[Effects of siRNA on expression of livin and dose- and time-response in human malignant melanoma LiBr cells].

AIM: To investigate the effects of siRNA on expression of livin and dose- and time-response in human malignant melanoma LiBr cells. METHODS: Three chemically synthesized specific siRNAs targeting to livin were transfected to LiBr cells, then the expression of livin was detected both at mRNA level by real-time RT-PCR and at protein level by Western blot, and the effective one was selected for use on observation of dose- and time-response to livin silencing. RESULTS: One of three designed siRNAs could effectively knock down the livin expression both at mRNA and protein levels in dose- and time- dependent manners, 100 nmol/L of which achieved the highest knockdown effect on mRNA at 48 h and on protein at 72 h after transfection. CONCLUSION: Expression of livin in LiBr cells could be efficiently knocked down by siRNA with target site 790-808 of livin mRNA.

Relapsing neuromyelitis optica and relapsing-remitting multiple sclerosis: differentiation at diffusion-tensor MR imaging of corpus callosum.

PURPOSE: To prospectively assess sensitivity and specificity of diffusion indexes of the corpus callosum (CC) for differentiating relapsing neuromyelitis optica (RNMO) from relapsing-remitting multiple sclerosis (RRMS), by using final clinical diagnosis as the reference standard. MATERIALS AND METHODS: Participants provided informed consent; the study was approved by the institutional review board. Forty-six consecutive patients with RRMS (18 men, 28 women; mean age, 37.7 years; range, 18-58 years) and 26 consecutive patients with RNMO (two men, 24 women; mean age, 38.6 years; range, 19-59 years) underwent diffusion-tensor magnetic resonance imaging. Mean diffusivity (MD) and fractional anisotropy (FA) of the region of interest (ROI) of the CC in the midsagittal plane were measured and used as discriminative indexes. Bayesian classification with leave-one-out cross-validation was used to determine diagnostic accuracy. Differences in diffusion indexes of ROIs among groups were evaluated by using the Kruskal-Wallis test, followed by the Mann-Whitney U test for multiple comparisons and Bonferroni correction. RESULTS: Mean MD (8.48 x 10(-4) mm(2)/sec) and FA (0.729) of the ROI in patients with RNMO were significantly (P<.001) different from those (MD=10.64 x 10(-4) mm(2)/sec, FA=0.599) in patients with RRMS. Sensitivity and specificity for differentiation were 92.3% (24 of 26 patients with RNMO) and 93.5% (43 of 46 patients with RRMS) for FA and 88.5% (23 of 26 patients with RNMO) and 89.1% (41 of 46 patients with RRMS) for MD, respectively. CONCLUSION: Measurement of diffusion indexes of the CC may be useful for distinguishing patients with RNMO from those with RRMS.

Ureteral intussusception due to a polyp.

Intussusception of the ureter is a rare complication of some ureteral diseases. A 49-year-old man was found to have a ureteral intussusception in the middle part of the right ureter accompanied by a polyp below the invaginated segment of the ureter. Surgery confirmed the diagnostic imaging findings. Here, we present a case of ureteral intussusception associated with a fibroepithelial polyp and discuss the radiological characteristics.

Diffusion tensor imaging in medial temporal lobe epilepsy.

BACKGROUND: Diffusion tensor imaging (DTI) is a noninvasive imaging technique for the assessment of the integrity of cerebral tissues. This study was undertaken to assess the changes of diffusion indices of hippocampal formation (HF) in patients with medial temporal lobe epilepsy (MTLE). METHODS: Fourteen patients with MTLE and 14 healthy subjects were evaluated. Mean diffusivity (MD) and fractional anisotropy (FA) from the symmetrical-voxel sampling regions of the anterior HF were calculated in all subjects. The MD and FA values were compared across the groups. RESULTS: No significant differences of MD and FA values were noted between right and left HF in the controls. In the patient group, MD significantly increased in the HF ipsilateral to the lesioned side [(9.27 +/- 1.09) x 10(-4) mm(2)/s], compared with the values in the contralateral HF [(8.20 +/- 0.59) x 10(-4) mm(2)/s] (t = 4.479, P = 0.001) and healthy subjects [(7.58 +/- 0.51) x 10(-4) mm(2)/s] (P < 0.001), but no significant differences were found in FA. When compared with the controls, patients had a significantly higher MD in the contralateral HF (P < 0.05), but the difference in FA was not statistically significant. CONCLUSIONS: DTI could detect hippocampal abnormality in patients with MTLE. This technique may be helpful for preoperative evaluation of such patients.

[Diffusion tensor imaging of the normal-appearing brain tissue in relapsing-remitting multiple sclerosis].

OBJECTIVE: To investigate whether normal-appearing brain tissue (NABT) on conventional MRI has occult damage in patients with relapsing-remitting multiple sclerosis (RRMS) by using diffusion tensor imaging (DTI) histogram analysis, and to determine the correlations between DTI histogram-derived measures of the NABT and expanded disability status scale (EDSS) scores, disease durations, T2WI lesion volumes and brain tissue volumes in RRMS patients. METHODS: Conventional MRI and DTI scans were performed in 24 patients with RRMS and 24 sex- and age-matched healthy controls. After segmentation of the NABT, the mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were created and analyzed. RESULTS: In patients with RRMS, the average MD (1.014 x 10(-3) mm2 x s(-1)) of the NABT was higher than that (0.910 x 10(-3) mm2 x s(-1)) of control subjects (t = 7.238, P < 0.001); the MD histogram peak height (8.858 per thousand) of the NABT was lower than that (0.767 per thousand) of control subjects (t = 6.161, P < 0.001); the MD histogram peak location (0.809 x 10(-3) mm2 x s(-1)) of the NABT was higher than that (0.767 x 10(-3) mm2 x s(-1)) of control subjects (t = 5.324, P < 0.001); the average FA (0.231) of the NABT was lower than that (0.254) of control subjects (t = 6.217, P < 0.001); the FA histogram peak height (4.502 per thousand) of the NABT was higher than that (4.107 per thousand) of control subjects (t = 4.198, P < 0.001); no significant difference was found in the FA histogram peak location of the NABT between these two groups (t = 1.223, P = 0.227); none of the DTI histogram-derived measures correlated with EDSS scores or disease durations (P > 0.05); the average MD and all the FA histogram-derived measures correlated with T2WI lesion volumes (P < 0.05); and the average MD, the MD histogram peak height and all the FA histogram-derived measures correlated with brain tissue volumes (P < 0.05). In healthy controls, however, only the average FA of the NABT correlated with brain tissue volumes. CONCLUSION: Patients with RRMS had occult damage in the NABT and the extent of NABT damage was related to the lesion load of brain and to the extent of brain tissue atrophy.

Diffusion tensor tractography in patients with cerebral tumors: a helpful technique for neurosurgical planning and postoperative assessment.

OBJECTIVE: To demonstrate the role of diffusion tensor tractography (DTT) in preoperative mapping of eloquent tracts in relation to cerebral tumors and to determine whether it is helpful for neurosurgical planning and postoperative assessment. METHODS AND MATERIALS: Sixteen patients with brain tumors underwent diffusion tensor imaging (DTI). The pyramidal tract, corpus callosum and optic radiation were reconstructed and the exact location of a lesion with respect to these tracts was observed to design a reasonable surgical plan for preserving vital tracts while maximizing tumor resection. After surgery, DTI was performed again and these tracts were evaluated to investigate the surgical outcomes. Twenty-four patients with suspicion of pyramidal tract involvement were also evaluated as a control group. RESULTS: The relationship between tracts and tumors was classified as three types: type I is simple displacement, type II is displacement with disruption and type III is simple disruption. Twelve cases involved in pyramidal tract (DTT group), one was type I with reduction of displacement after surgery, nine were type II with reduction of displacement and other two were type III without any improvement. The extent of tumor resection (p = 0.045) and postoperative improvement of locomotive function (p = 0.015) of DTT group were significantly higher than those of control group. Corpus callosum was involved in seven cases, three were type II with reduction of displacement and four were type III without any improvement. Optic radiation was involved in three cases, all were type I with reduction of displacement. CONCLUSION: DTT allowed for visualization of the exact location of tumors relevant to eloquent tracts and was found to be beneficial in the neurosurgical planning and postoperative assessment.