Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.
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.
At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.
Aim: Inflammation plays a role in secondary brain injury after intracerebral hemorrhage (ICH). We aimed to determine the prognostic significance of admission white blood cell (AWC), neutrophil count (ANC), lymphocyte count, monocyte count and neutrophil to lymphocyte ratio (NLR) for 90-day outcome after ICH. Patients & methods: A total of 336 patients with spontaneous ICH were retrospectively investigated. Clinical outcome was assessed by modified Rankin Scale at 90 days. Results: Multivariate analysis showed that higher AWC, ANC, NLR were independently associated with mortality and worse outcome. Moreover, NLR showed a higher predictive ability in mortality than in poor outcome in receiver operating characteristic analysis. Linear regression analyses revealed admission Glasgow Coma Scale score and ICH volume were mostly correlated with these indices. Conclusion: Elevated levels of AWC, ANC and NLR were independently related to poor 90-day outcome after ICH. NLR may be a novel inflammatory biomarker following ICH.
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.
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.
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.
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.
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.
The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 +/- 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including EnbrelA (R) and local brand Yi Sai PuA (R) and QiangkeA (R)), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 +/- 15.6 mg for 25.5 +/- 47.0 weeks and tocilizumab at 94.5 +/- 21.9 mg for 4.7 +/- 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for < 3 months, those receiving bDMARDs for 3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for 12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.
