In vivo imaging of neuroblastomas using GD2-targeting graphene quantum dots

BackgroundPatients with neuroblastoma, a common childhood malignancy, often have poor prognosis. It is mandatory to develop an accurate and efficient diagnostic tool for neuroblastomas, so that the treatment can be started early. Graphene quantum dot (GQD), a nanomaterial, can be used to carry proteins, genetic materials, or drugs. GD2, a disialoganglioside, is a surface antigen expressed on neuroblastoma. This study investigated the in vivo targeting and imaging of neuroblastomas using GD2-targeting GQDs.MethodsGQDs were synthesized and conjugated with anti-GD2 antibody (anti-GD2/GQDs). In vitro cytotoxicity of GQDs and anti-GD2/GQDs was studied in human neuroblastoma cells by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide)-based colorimetric assay. The tumor tracking and imaging of anti-GD2/GQDs in mice were investigated by in vivo imaging system (IVIS).ResultsTreatment with GQDs or anti-GD2/GQDs induced no or mild cytotoxicity in fibroblasts and neuroblastoma cells. After co-incubation, GQDs and anti-GD2/GQDs were located in the cytoplasm and nucleus of neuroblastoma cells, with GQDs showing a blue fluorescence and anti-GD2/GQDs an orange/red emission. The IVIS images demonstrated accumulation of the fluorescence of anti-GD2/GQDs in the subcutaneous tumors in mice 24 h after intravenous injection of anti-GD2/GQDs.ConclusionsAnti-GD2/GQDs may potentially be used for the targeting and imaging of neuroblastomas in vivo.     

Tourette syndrome associated with Page kidney

Clinical and Experimental Nephrology - Page kidney is a rare condition leading to secondary hypertension and encountered most frequently due to traumatic subcapsular hematoma. Here, we present a...     

Tension band plates have greater risks of complications in temporary epiphysiodesis

PurposeThis study aimed to compare the efficacy of decreasing leg-length discrepancy (LLD) and postoperative complications between tension band plates (TBP) and percutaneous transphyseal screws (PETS).MethodsThis retrospective study reviewed LLD patients who underwent temporary epiphysiodesis at the distal femur and/or proximal tibia from 2010 to 2017 (minimum two years follow-up). Efficacy of decreasing LLD was assessed one and two years postoperatively. Complications were classified with the modified Clavien-Dindo-Sink complication classification system. Knee deformities were assessed by percentile and zone of mechanical axis across the tibial plateau.ResultsIn total, 53 patients (25 boys, 28 girls) underwent temporary epiphysiodesis (mean age, 11.4 years). The efficacy of decreasing LLD at two years between the TBP (n = 38) and PETS (n = 15) groups was comparable. Seven grade III complications were recorded in six TBP patients and in one PETS patient who underwent revision surgeries for knee deformities and physis impingement. Four grade I and two grade II complications occurred in the TBP group. The mechanical axis of the leg shifted laterally in the PETS group and medially in the TBP groups (+7.1 percentile versus -4.2 percentile; p < 0.05). Shifting of the mechanical axis by two zones was noted medially in four TBP patients and laterally in two PETS patients.ConclusionMore implant-related complications and revision surgeries for angular deformities were associated with TBP. A tendency of varus and valgus deformity after epiphysiodesis using TBP and PETS was observed, respectively. Patients and families should be informed of the risks and regular postoperative follow-up is recommended.Level of evidenceLevel III     

SC phocomelia syndrome, premature centromere separation, and congenital cranial nerve paralysis in two sisters, one with malignant melanoma

Two middle age sisters had most manifestations of the SC phocomelia syndrome including postnatal growth retardation, symmetric limb deficiencies with radial aplasia and absent thumbs, facial anomalies with microcephaly, microphthalmia, hypoplastic nasal alae, and borderline to mild mental retardation. Unusual findings included congenital paralysis of some cranial nerves in both patients and malignant melanoma in the proposita. Cultured lymphocytes from both patients, and skin fibroblasts, Epstein Barr virus-transformed lymphocytes, and tumor cells from the proposita demonstrated premature separation of centromeric heterochromatin (PCS) of many chromosomes, a finding noted previously in the SC phocomelia syndrome and the similar but more severe Roberts syndrome. Extensive overlap of the phenotypes of the sisters and 15 other patients with either syndrome and PCS confirms that these are either allelic conditions or the same disease--designated Roberts-SC phocomelia syndrome. The role of PCS in the syndrome(s) remains uncertain since some patients with the characteristic clinical phenotypes are reported to lack it.     

Growth suppression of human colorectal carcinoma in nude mice by monoclonal antibody C27-abrin A chain conjugate

PURPOSE: The aim of this study was to assess an immunotoxin, monoclonal antibody C27-abrin A chain conjugate (MAAC), that might be effective in the treatment of colorectal carcinoma. METHODS: The immunotoxin was prepared by a specific monoclonal antibody against carcinoembryonic antigen (CEA), monoclonal antibody C27, linked toN-succinimidyl-3-(2-pyridyldithio)propionate and then coupled covalently to the toxic abrin-A chain to synthesize MAAC. The therapeutic role of this immunotoxin in suppressing thein vitro andin vivo growth of CEA-secreting human colorectal cancer cells (LS174T) was assayed by methods of protein biosynthesis inhibition, cell colony proliferation, and treatment of tumor cells before and after inoculation in nude mice. RESULTS: We found that MAAC effectively suppressed the growth of LS174T in culture medium and completely eradicated cells in inoculated nude mice. In contrast, irrelevant immunotoxin antiferritin-abrin A chain conjugate and isotype-matched monoclonal immunoglobin (MOPC21IgG1)-abrin A chain conjugate did not cause such effects. Thein vitro toxicity was highly specific because the conjugate (MAAC) inhibitedde novo protein biosynthesis, impeded growth, and caused death of cells possessing surface CEA determinants. The 50 percent inhibition dose values of the conjugate for colonogenic survival and for protein biosynthesis in LS174T cells were 0.09 g/ml and 0.06 g/ml, respectively. Colony survival was inhibited 96.3 percent after prolonged MAAC treatment. MAAC showed selective cytotoxicity; the inhibitory effect of MAAC to the CEA-secreting LS174T cells over the CEA-nonsecreting human embryonic kidney cells was 16-fold. CONCLUSION: These results indicate that MAAC may be of benefit in therapy during or soon after resection of colorectal carcinoma or in patients who have micrometastasis.Supported by a grant from the National Science Council and the Veterans General Hospital-Taipei, Taipei, Taiwan.     

Effect of dynamization on gap healing of diaphyseal fractures under external fixation

We asked whether dynamization of externally fixed diaphyseal fractures could improve bone healing in comparison to rigid fixation of fractures having similar remaining gap sizes. To answer this question we evaluated metatarsal osteotomies in 12 sheep. The osteotomy with a 0.6-mm gap was stabilized with a specially designed high bending and torsional stiffness external ring fixator. Osteotomies in six sheep were stabilized rigidly (axial movement < 0.06 mm) or dynamically (axial movement 0.15-0.34 mm). The cyclical axial interfragmentary movement was caused by the load-bearing of the operated limb. With increasing healing time, the initially allowed movement was decreased by callus formation around the osteotomy. The reduction in interfragmentary movement was measured and monitored by a linear variable displacement transducer at the external fixator and a telemetry system. After 9 weeks the sheep were sacrificed and the healed bones were investigated biomechanically and histomorphologically. Compared to the rigidly fixed osteotomies, the dynamized osteotomies showed significantly (P < 0.05) greater (+41%) callus formation and 45% greater tensile strength of the newly formed bone in the cortical osteotomy gap. Histological analysis indicated that the effect of dynamization occurred mainly after the 5th week. RELEVANCE: From these results we conclude that dynamic fixation of diaphyseal gaps is advantageous in comparison to stable external fixation.     

Differential regulation of EGF production, EGF receptor-binding, and cellular growth by sodium-butyrate in hep3b and plc/prf/5 human hepatoma-cells

Hep3B and PLC/PRF/5 human hepatoma cells express epidermal growth factor (ECF) mRNA and secret this polypeptide growth factor into the culture medium. The production of EGF was inhibited by sodium butyrate in a dose-dependent manner. EGF receptor numbers in both cell lines were increased after treatment with butyrate for 2 days, In addition, the binding affinity of EGF to its receptor was decreased in butyrate-treated PLC/PRF/5 cells while it did not change in Hep3B cells. EGF-stimulated cell growth in PLC/PRF/5 cells was attenuated by sodium butyrate whereas no significant inhibition df cell growth of Hep3B cells was found in the same condition. Our results suggest that EGF acts as an autocrine growth stimulator in human hepatoma cells and sodium butyrate can differentially regulate the responses of hepatoma cells to EGF by modulating the differentiation states of these cells.     

Rectal cancer mortality and total hardness levels in Taiwan's drinking water.

The possible association between the risk of rectal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (986 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and rectal cancer mortality. Odds ratio and 95% confidence intervals were 1.24 (1.01-1. 55) and 1.38 (1.10-1.73), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for rectal cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.     

Fungal corneal ulcers of onion harvesters in southern Taiwan

Fungal corneal ulcers related to agriculture has been reported throughout the world, especially in tropical areas. Most of them were sporadic and had histories of ocular trauma or use of topical corticosteroids and topical antibiotics. Five onion harvesters had fungal corneal ulcers during the same harvest period in Southern Taiwan. The authors think that this is the first report of a group occurrence relating to agricultural workers. Although all of the patients improved after medical and surgical management, their vision was greatly decreased. It is suggested that the tropical climate, the harvest procedure, the characteristic monsoon, and lack of eye protection were involved. Therefore, the importance of the eye protection, hygiene education, and improving medical care to reduce the occurrence of fungal corneal ulcer in agriculture workers must be emphasised.