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1.
Sono-Photodynamic therapy (SPDT), a new modality for cancer treatment, is aimed at enhancing anticancer effects by the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we investigated the antitumor effect and possible mechanisms of Chlorin e6 (Ce6) mediated SPDT (Ce6-SPDT) on breast cancer both in vitro and in vivo. MTT assay revealed that the combined therapy markedly enhanced cell viability loss of breast cancer cell lines (MDA-MB-231, MCF-7 and 4T1) compared with SDT and PDT alone. Propidium iodide/hoechst33342 double staining reflected that 4T1 cells with apoptotic morphological characteristics were significantly increased in groups given combined therapy. Besides, the combined therapy caused obvious mitochondrial membrane potential (MMP) loss at early 1 h post SPDT treatment. The generation of intracellular reactive oxygen species (ROS) detected by flow cytometry was greatly increased in 4T1 cells treated with the combination therapy, and the loss of cell viability and MMP could be effectively rescued by pre-treatment with the ROS scavenger N-acetylcysteine (NAC). Further, Ce6-SPDT markedly inhibited the tumor growth (volume and weight) and lung metastasis in 4T1 tumor-bearing mice, but had no effect on the body weight. Hematoxylin and eosin staining revealed obvious tissue destruction with large spaces in the Ce6-SPDT groups, and TUNEL staining indicated tumor cell apoptosis after treatment. Immunohistochemistry analysis showed that the expression level of VEGF and MMP were significantly decreased in the combined groups. These results indicated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, loss of MMP and generation of ROS might be involved. In addition, Ce6-mediated SPDT significantly inhibited tumor growth and metastasis in mouse breast cancer 4T1 xenograft model, in which MMP-9 and VEGF may play a crucial role.  相似文献   

2.

Background

Autophagy, an intracellular response to stress, is characterized by double membrane cytosolic vesicles called autophagosomes. Prolonged autophagy is known to result in autophagic (Type II) cell death. This study examined the potential role of an autophagic response in cultured cerebellar granule neurons challenged with excitotoxin N-methyl-D-aspartate (NMDA).

Results

NMDA exposure induced light chain-3 (LC-3)-immunopositive and monodansylcadaverine (MDC) fluorescent dye-labeled autophagosome formation in both cell bodies and neurites as early as 3 hours post-treatment. Elevated levels of Beclin-1 and the autophagosome-targeting LC3-II were also observed following NMDA exposure. Prolonged exposure of the cultures to NMDA (8-24 h) generated MDC-, LC3-positive autophagosomal bodies, concomitant with the neurodegenerative phase of NMDA challenge. Lysosomal inhibition studies also suggest that NMDA-treatment diverted the autophagosome-associated LC3-II from the normal lysosomal degradation pathway. Autophagy inhibitor 3-methyladenine significantly reduced NMDA-induced LC3-II/LC3-I ratio increase, accumulation of autophagosomes, and suppressed NMDA-mediated neuronal death. ATG7 siRNA studies also showed neuroprotective effects following NMDA treatment.

Conclusions

Collectively, this study shows that autophagy machinery is robustly induced in cultured neurons subjected to prolonged exposure to excitotoxin, while autophagosome clearance by lysosomal pathway might be impaired. Our data further show that prolonged autophagy contributes to cell death in NMDA-mediated excitotoxicity.  相似文献   

3.

Objectives

The present study aims to investigate apoptosis of human leukemia K562 cells induced by protoporphyrin IX (PpIX)-mediated sonodynamic therapy (PpIX-SDT).

Methods

The uptakes of intracellular PpIX in K562 cells were detected by flow cytometry. The sub-cellular localization of PpIX was imaged by confocal microscope. The cytotoxic effect of PpIX-SDT was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenylter-trazolium bromide tetrazolium) assay. Apoptosis was evaluated by chromatin condensation with DAPI (4′-6-diamidino-2-phenylindole) staining, decrease of mitochondria membrane potential (MMP), re-distribution of Bax, and the expression changes of the key apoptosis-associated protein (Caspase-3 and polypeptide poly (ADP-robose) polymerase). The possible mechanism of SDT-induced apoptosis was investigated by detecting by intracellular ROS (reactive oxygen species) generation and effect of ROS scavenger-NAC (N-acetylcysteine) on SDT induced apoptosis.

Results

The intracellular PpIX increased quickly within 2 h after PpIX administration and PpIX mainly localized in the mitochondria. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound was significantly boosted. In addition, the ultrasound induced some extent of chromatin condensation and MMP loss was greatly enhanced by the presence of 2 μg/ml PpIX, where PpIX alone treatment showed no or only slight effect. Time-dependent Bax translocation, caspase-3 activation and PARP cleavage were detected in SDT treatment groups. Besides, intracellular ROS production was significantly enhanced after SDT, and the general ROS scavenger NAC could obviously alleviate the SDT-caused cell viability loss, MMP loss, Bax redistribution and nuclear changes.

Conclusions

These results indicated that PpIX-mediated sonodynamic action could induce apoptosis on K562 cells, and the intracellular ROS was involved in the PpIX-SDT induced apoptosis.  相似文献   

4.

Objective

Equivalent cross-relaxation rate imaging (ECRI) is an MRI technique used to evaluate qualitative changes in protein-water interactions. We aimed to prospectively evaluate the utility of ECRI for classification of adipocytic tumors.

Materials and Methods

Institutional Review Board approval was obtained and all patients provided informed consent. Study participants included 40 patients with adipocytic tumors who were diagnosed with lipomas (n = 22), atypical lipomatous tissue/well-differentiated liposarcoma (ALT/WDL; n = 9), myxoid/round cell liposarcoma (MyL; n = 6), and dedifferentiated liposarcoma (DDL; n = 3), and 20 control patients for whom subcutaneous fat in the buttock or thigh was analyzed.

Results

Mean ECR values of lipomas, ALT/WDL, and subcutaneous fat were low, and those of MyL and DDL were high. Mean ECR values of MyL and DDL were significantly higher than those of ALT/WDL. The cut-off value was 5.1%. There was a positive correlation between ECR value, pathological grade, and cell density in adipocytic tumors.

Conclusion

The ECR value positively correlates with pathological grade and cell density of adipocytic tumors. Our findings suggest that ECRI is a useful method for preoperative evaluation of adipocytic tumors.  相似文献   

5.

Purpose

To investigate the value of apparent diffusion coefficient (ADC) to predict and monitor the therapy response for cervical cancer patients receiving concurrent radiochemotherapy, and to analyze the influence of different b-value combinations on ADC-based evaluation of treatment response.

Material and Methods

Seventy-five cervical cancer patients treated with radiochemotherapy received conventional MRI and DWI prior to therapy, after 2 weeks of therapy, after four weeks of therapy and after therapy completion. Treatment response was classified as complete response (CR, n = 35), partial response (PR, n = 22) and stable disease (SD, n = 18), which was determined according to final tumor size after 6 months of therapy completion. Dynamic changes of apparent diffusion coefficients (ADC) and tumor size in the three tumor groups were observed and compared. All the ADCs were calculated from b = 0, 600 s/mm2 and b = 0, 1000 s/mm2.

Results

The ADC increased percentage was higher in CR group than those in PR and SD groups after two weeks and four weeks of therapy, with significant differences in absolute ADCs between CR and PR, SD groups after therapy completion; the overall discriminatory capability for differentiation of CR and PR, SD groups was higher for high b-value combination (0, 1000 s/mm2) than for low b-value combination (0, 600 s/mm2).

Conclusion

DWI can be used as a predictive and monitoring biomarker of treatment response to radiochemotherapy in patients with cervical cancer. High b-value combination may be more reliable to evaluate the treatment response for cervical cancer.  相似文献   

6.

Objective

Development of a fast 3D high-resolution magnetic resonance imaging (MRI) protocol for improved carotid artery plaque imaging.

Methods

Two patients with carotid atherosclerosis disease underwent 3D high-resolution MRI which included time-of-flight and T1-weighted variable flip angle, fast-spin-echo (FSE) imaging, pre- and post-intravenous gadolinium-based contrast agent administration.

Results

Good quality images with intrinsic blood suppression were obtained pre- and post-contrast administration using a 3D FSE sequence. The plaque burden, lipid core volume, hemorrhage volume and fibrous cap thickness were well determined.

Conclusions

3D high-resolution MR imaging of carotid plaque using TOF and 3D FSE can achieve high isotropic resolution, large coverage, and excellent image quality within a short acquisition time.  相似文献   

7.

Purpose

To investigate intracranial microvascular images with transceiver radio-frequency (RF) coils at ultra-high field 7 T magnetic resonance imaging (MRI).

Materials and methods

We designed several types of RF coils for the study of 7 T magnetic resonance angiography and analyzed quantitatively each coil's performance in terms of the signal-to-noise ratio (SNR) profiles to evaluate the usefulness of RF coils for microvascular imaging applications. We also obtained the microvascular images with different resolutions and parallel imaging technique.

Results

The overlapped 6-channel (ch) transceiver coil exhibited the highest performance for angiographic imaging. Although other multi-channel coils, such as 4- or 8-ch, were also suitable for fast imaging, these coils performed poorly in homogeneity or SNR for angiographic imaging. Furthermore, the 8-ch coil was poor in SNR at the center of the brain, while it had the highest SNR at the periphery.

Conclusion

The present study has demonstrated that the overlapped 6-ch coil with large-size loop coils provided the best performance for microvascular imaging or angiography with the ultra-high-field 7 T MRI, mainly because of its long penetration depth together with high SNR.  相似文献   

8.

Purpose

To optimize the navigator-gating technique for the acquisition of high-quality three-dimensional spoiled gradient-recalled echo (3D SPGR) images of the liver during free breathing.

Materials and methods

Ten healthy volunteers underwent 3D SPGR magnetic resonance imaging of the liver using a conventional navigator-gated 3D SPGR (cNAV-3D-SPGR) sequence or an enhanced navigator-gated 3D SPGR (eNAV-3D-SPGR) sequence. No exogenous contrast agent was used. A 20-ms wait period was inserted between the 3D SPGR acquisition component and navigator component of the eNAV-3D-SPGR sequence to allow T1 recovery. Visual evaluation and calculation of the signal-to-noise ratio were performed to compare image quality between the imaging techniques.

Result

The eNAV-3D-SPGR sequence provided better noise properties than the cNAV-3D-SPGR sequence visually and quantitatively. Navigator gating with an acceptance window of 2 mm effectively inhibited respiratory motion artifacts. The widening of the window to 6 mm shortened the acquisition time but increased motion artifacts, resulting in degradation of overall image quality. Neither slice tracking nor incorporation of short breath holding successfully compensated for the widening of the window.

Conclusion

The eNAV-3D-SPGR sequence with an acceptance window of 2 mm provides high-quality 3D SPGR images of the liver.  相似文献   

9.

Objective

This study was conducted to evaluate, with micro-computed tomography, the influence of low-intensity pulsed ultrasound on wound-healing in periodontal tissues.

Methods

Periodontal disease with Class II furcation involvement was surgically produced at the bilateral mandibular premolars in 8 adult male beagle dogs. Twenty-four teeth were randomly assigned among 4 groups (G): G1, periodontal flap surgery; G2, periodontal flap surgery + low-intensity pulsed ultrasound (LIPUS); G3, guided tissue regeneration (GTR) surgery; G4, GTR surgery plus LIPUS. The affected area in the experimental group was exposed to LIPUS. At 6 and 8 weeks, the X-ray images of regenerated teeth were referred to micro-CT scanning for 3-D measurement.

Results

Bone volume (BV), bone surface (BS), and number of trabeculae (Tb) in G2 and G4 were higher than in G1 and G3 (p < 0.05). BV, BS, and Tb.N of the GTR + LIPUS group were higher than in the GTR group. BV, BS, and Tb.N of the LIPUS group were higher than in the periodontal flap surgery group.

Conclusion

LIPUS irradiation increased the number, volume, and area of new alveolar bone trabeculae. LIPUS has the potential to promote the repair of periodontal tissue, and may work effectively if combined with GTR.  相似文献   

10.

Purpose

To report the observation of brown adipose tissue (BAT) with low fat content in neonates with hypoxic–ischemic encephalopathy (HIE) after they have undergone hypothermia therapy.

Materials and Methods

The local ethics committee approved the imaging study. Ten HIE neonates (3 males, 7 females, age range: 2–3 days) were studied on a 3-T MRI system using a low-flip-angle (3°) six-echo proton-density-weighted chemical-shift-encoded water-fat pulse sequence. Fat-signal fraction (FF) measurements of supraclavicular and interscapular (nape) BAT and adjacent subcutaneous white adipose tissues (WAT) were compared to those from five non-HIE neonates, two recruited for the present investigation and three from a previous study.

Results

In HIE neonates, the FF range for the supraclavicular, interscapular, and subcutaneous regions was 10.3%–29.9%, 28.0%–57.9%, and 62.6%–88.0%, respectively. In non-HIE neonates, the values were 23.7%–42.2% (p = 0.01), 45.4%–59.5% (p = 0.06), and 67.8%–86.3% (p = 0.38), respectively. On an individual basis, supraclavicular BAT FF was consistently the lowest, interscapular BAT values were higher, and subcutaneous WAT values were the highest (p < 0.01).

Conclusion

We speculate that hypothermia therapy in HIE neonates likely promotes BAT-mediated non-shivering thermogenesis, which subsequently leads to a depletion of the tissue's intracellular fat stores. We believe that this is consequently reflected in lower FF values, particularly in the supraclavicular BAT depot, in contrast to non-HIE neonates.  相似文献   

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