Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs), but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM), a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7), and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.
Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25-30g) and divided into SMF+force group, force group, and no force group. Exposure time was over 22h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down-regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22-30, 2017. (c) 2016 Wiley Periodicals, Inc.
Deferoxamine (DFO), an iron chelator, is commonly used to remove excess iron from the body. DFO has also been demonstrated to have anti-tumor effect. However, there is no available report on the effect of deferoxamine on mesenchymal stromal cells (MSCs). In this study, we first isolated tumor-associated MSCs (TAMSCs) from EG-7 tumors, which were positive for CD29, CD44, CD73, CD90 and CD105. Ex vivo cultured stem cells derived from tumor and bone marrow compartment were exposed to DFO. We demonstrated that DFO had growth-arresting and apoptosis-inducing effect on TAMSCs and bone marrow MSCs (BMMSCs). DFO also influenced the expression pattern of adhesion molecule VCAM-1 on both TAMSCs and BMMSCs. Notwithstanding its widespread use, our results here warrants caution in the application of DFO, and also highlights the need for careful evaluation of the bone marrow compartment in patients receiving DFO treatment. (C) 2016 Elsevier B.V. All rights reserved.
alpha-Calcitonin gene-related peptide (alpha-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of alpha-CGRP in plasma is only 10 min, which affects its long-time application and an alternative approach should be developed to deliver alpha-CGRP over long periods of time. The aim of this study is to investigate whether a lentiviral alpha-CGRP overexpression vector system can express this target-gene longer at peri-implant sites, thus enhancing osseointegration. Animals were divided to the following groups: alpha-CGRP(-/-), alpha-CGRP(-/-) with lentivirus transfection and alpha-CGRP(+/+) mice. MS Spectrum imaging observations identified the successful transfection of alpha-CGRP around experimental implants inserted in the femurs at 5 days after injection. Histomorphometrical analysis indicated an increase of bone-implant contact (BIC) at 1-month healing in the transfection group. Moreover, real-time RT-PCR and western blot results of bone-related markers Runx2, Osterix, and BSP levels elevated in lentivirus-transfected mice at 21 days, compared to the untreated alpha-CGRP(-/-) mice. There was no significant difference between the transfection group and alpha-CGRP(+/+) group. Further alpha-CGRP protein detection confirmed the persistent expression of this transgene at 21 days post-operatively. These results suggest that this lentiviral vector system expresses alpha-CGRP in an effective, appropriate and sustained manner, which might have a potential application in enhancing titanium implant osseointegration. (C) 2016 Elsevier Inc. All rights reserved.
ObjectivesThis study investigated the prevalence, etiology, assessment, treatment of pain in patients with cancer as well as their quality of life (QOL).
MethodsPatients at the West China Hospital Cancer Center were invited to complete a questionnaire under the guidance of pain specialists. The questionnaire included general information, cancer pain status, its assessment, use of analgesics, and the effects of pain on QOL.
ResultsIn total, 1,050 patients were enrolled in the study. Of these, valid data were collected from 919 patients, among whom 454 (49.4%) suffered from pain, including 333 (36.2%) patients who had neuropathic pain symptoms. On average, the visual analog scale (VAS) score of patients with cancer pain was 3.30 1.68. Significant differences in the VAS score and pain frequency between patients with nociceptive and neuropathic pain were observed (both P < 0.05). Dull pain ranked first (64, 52.9%) among the patients with nociceptive pain, whereas pins and needles pain (97, 64.7%) was the most common type of pain in patients with neuropathic pain. There was a significant difference in QOL between the nociceptive and neuropathic pain groups (P < 0.05). Only 183 of 454 patients with cancer pain used analgesics. Compared with the patients with pain not using any analgesics, those receiving analgesics had a significantly lower average pain relief rate (P = 0.027). Adjuvant analgesics were inadequately used (9.3%) in patients with neuropathic cancer pain.
ConclusionThis study revealed the prevalence of neuropathic cancer pain in Chinese patients with cancer. Malignant neuropathic pain significantly impaired the patients' QOL. Insufficient assessment and inadequate analgesia still exist. These require more awareness and attention from both doctors and patients.
Objectives: Antihypertensive therapy is effective to control blood pressure (BP) and to prevent cardiovascular events, but the further treatment strategies for patients who cannot achieve goal BP with low-dose monotherapy is still under dispute. Our study investigates the effects of high-dose amlodipine and valsartan and their low-dose combination on blood pressure variability (BPV) and pulse wave velocity (PWV) to provide references for clinical medication.
Materials and Methods: This study was a prospective, randomized, parallel, case-controlled trial performed in a medical center. A total of 134 outpatients newly diagnosed with essential hypertension or receiving low-dose monotherapy were enrolled and 119 completed the trial. They were randomized into amlodipine 10 mg group (n = 40), valsartan 160 mg group (n = 38) and amlodipine 5 mg + valsartan 80 mg (n = 41) in a 1:1:1 allocation ratio for a 10-week treatment. Demographic data and laboratory indicators were collected at the randomization and 10 weeks after the treatment. The 24-hour ambulatory BP and brachial-ankle PWV were also monitored.
Results: All therapies reduced systolic and diastolic BP (P < 0.05). The 24-hour systolic BPV was significantly decreased in amlodipine and combination groups (3.55 +/- 2.57, 4.11 +/- 2.20 versus 2.23 +/- 2.54 mm Hg, P < 0.05). The effects on diastolic BPV differed between different treatments. PWV was lowered by 3 antihypertensive schemes; the degree of which from strongest to weakest were valsartan, combination and amlodipine (228.87 +/- 60.41 versus 152.49 +/- 49.25 versus 99.35 +/- 35.57 cm/second, P < 0.01).
Conclusions: All further strategies can effectively control BP. The combination treatment reduces both BPV and PWV noticeably, whereas double-dose amlodipine achieves the greatest BPV decrease and valsartan is best in controlling PWV.
Background and Aim: A matched-pair comparison was performed to compare the efficacy and safety of sublobar resection versus radiotherapy for high-risk elderly patients with Stage I non-small cell lung cancer (NSCLC).
Patients and Methods: We searched the Cochrane Library, MEDLINE, CENTRAL, EMBASE and manual searches. The meta-analysis was performed to compare overall survival, pattern of failure, and toxicity among the homogeneous studies. Subdivided analyses were also performed.
Results: Sixteen studies containing 11540 patients were included in the meta-analysis. Among these studies, 9 were propensity-score matched (PSM) cohort studies, and 7 were cohort studies. Sublobar resection, compared with radiotherapy (either conventional fraction radiation therapy or stereotactic body radiation therapy), significantly improved the overall survival regardless in both PSM and non-PSM analyses (all p < 0.05). However, the difference in the pattern of failure and toxicity were not significant (all p > 0.05).
Conclusions: Sublobar resection was associated with improved outcomes in high-risk elderly patients with Stage I NSCLC, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials.
Epirubicin (EPI) is one of the most widely used anticarcinogens; however, serious side effects, including cardiomyopathy and congestive heart failure, limit its long-term administration. To overcome this problem, the HAIYPRH peptide ligand was used with EPI in the synthesis of a HAIYPRH-EPI conjugate. The anticancer activity and cellular uptake of the conjugate were measured and evaluated. The results of the present study indicated that the cytotoxicity of HAIYPRH-EPI was correlated with the expression of the cell surface transferrin receptor (TfR). The conjugate exerted high cytotoxicity and proapoptotic function when in an LN229 glioma cell line, which overexpresses surface TfR. It was hypothesized that transferrin (Tf) can promote cytotoxicity. Conversely, the conjugate exhibited very low cytotoxicity and proapoptotic function in a U87 glioma cell line, in which surface TfR expression was undetectable. In addition, fluorescence microscopy and flow cytometry methods were used to evaluate cellular uptake, and the results of these methods were consistent with the present hypotheses. The conjugate cellular uptake of the conjugate in LN229 cells was markedly higher compared with that in U87 cells, and it was hypothesized that Tf can enhance the uptake in LN229 cells. The cytotoxicity of HAIYPRH-EPI was dependent upon the expression of surface TfR. Considering that the majority of cancer cells have high rates of iron uptake and surface TfR is generally overexpressed on cancer cells, it was speculated by the authors that HAIYPRH-EPI may form part of an effective strategy for increasing the selectivity of EPI for cancer cells, as well as reducing its systemic toxicity. To confirm the hypothesis, the effects of HAIYPRH-EPI on non-cancerous cell lines were investigated. A future study will examine the side effects of HAIYPRH-EPI, using a suitable delivery system in an animal model.
Objective To determine oxidative stress status and its association with clinical and metabolic parameters in Chinese women with different clinical phenotypes of polycystic ovary syndrome (PCOS).
Design A cross-sectional study.
Patients A total of 544 patients with PCOS and 468 control women were included.
Measurements The total oxidant status (TOS) was determined using a microplate colorimetric method. Total antioxidant capacity (T-AOC), oxidative stress index (OSI, the ratios of TOS to T-AOC) and clinical, hormonal and metabolic parameters were also analysed.
Results TOS and OSI were significantly higher in each of the four PCOS phenotypes based on the Rotterdam criteria than in the control women and higher in patients with hyperandrogenism (HA) than in those without HA (P < 0.05). TOS, T-AOC and OSI were higher in lean patients than in lean controls (P < 0.05). These values, except OSI, were also higher in overweight/obese patients than in lean patients, and lean or overweight/obese controls (P < 0.05). Multivariate regression analysis demonstrated that apolipoprotein (apo) A1, the Ferriman-Gallwey score, triglyceride (TG), oestradiol (E-2), high-density lipoprotein cholesterol (HDL-C) and 2-h glucose levels were the main predictors of TOS; the Ferriman-Gallwey score, E-2, apoA1, TG and HDL-C levels were the main predictors of OSI.
Conclusions Patients with PCOS with HA have higher oxidative stress levels compared with those without HA. The increased oxidative stress in PCOS is related to HA status, increased plasma glucose, TG, HDL-C and E2 levels, decreased apoA1 concentrations and a relative shortage of antioxidant capacity.
Objective Postablation whole-body scintigraphy, which is performed 5-7 days after administration of ablation activity of radioactive iodine-131 (I-131) in patients with thyroid cancer, is considered a routine procedure for remnant ablation and a useful tool for disease staging. However, the relationship of preablation stimulated thyroglobulin (s-Tg) levels with postablation scintigraphic findings has not been evaluated. The current study was designed to determine the diagnostic value of postablation I-131 scintigraphy during initial staging and risk stratification in intermediate-risk papillary thyroid cancer (PTC) patients with pre-ablation s-Tg < 1 ng/ml at the time of ablation.
Design From January 2013 to July 2015, consecutive PTC patients at intermediate-risk of recurrence according to American Thyroid Association criteria were prospectively recruited. Patients had to have pre-ablation s-Tg < 1 ng/ml in the absence of anti-Tg antibody at the time of ablation. Systematic pre-ablation neck ultrasonography was performed for each patient. Postablation whole-body planar scintigraphy was obtained 5 days after administration of ablation activity of I-131. Single photon emission computed tomography/low-dose computed tomography was added for patients whose planar findings were inconclusive.
Results Among 756 patients ablated, 240 (31.7%) patients were eligible for the analysis. Pre-ablation neck ultrasonography revealed lymph node metastases in eight of the 240 patients. Postablation scintigraphy showed ectopic neck uptake corresponding to the lymph nodes seen by ultrasonography in four patients and revealed neck lymph node metastases in another two patients whose ultrasonography findings were negative. None of the 240 patients showed distant metastasis on postablation scintigraphy. Neither staging nor initial risk stratification was altered by postablation scintigraphy in the included patients with pre-ablation s-Tg < 1 ng/ml.
Conclusions As postablation whole-body scintigraphy played a minimal role in improving staging or initial risk stratification in intermediate-risk PTC patients with pre-ablation s-Tg < 1 ng/ml, we propose that postablation scintigraphy may be omitted in this group of patients. Multi-institutional larger studies are necessary to draw definitive conclusions.
