Activity of gelatins to induce secretion of a variety of cytokines from murine peritoneal exudate macrophages

Previously, we observed that liquid form bovine bone (BB) gelatin stimulates murine spleen cells to proliferate in vitro. In this study, activity of BB gelatin to stimulate murine-adherent peritoneal exudate cells (PEC) to secrete cytokines has been examined. Quantitatively, BB gelatin stimulated adherent PEC of C3H/HeN mice to secrete interleukin (IL)-12 (+p40), TNF-alpha, and IL-6 but not IL-1beta, IL-2, IL-10, and IFN-gamma. Qualitatively, BB gelatin-induced secretion of KC, MIP-2, MCP-1, RANTES, and MIP-1a as well as IL-6 but not 6Ckine, CTACK, Eotaxin, G-CSF, GM-CSF, IL-2,-3,-4,-5,-9,-10,-12,-13,-17, Leptin, IFN-gamma, SCF, sTNFri, TARC, TNF-alpha, TIMP-1, Tpo, and VEGF. BB gelatin acted on adherent PEC of C3H/HeN mice but not C3H/HeJ mice, which lack Toll-like receptor 4. Polymyxin B, a LPS antagonist, did not inhibit the activity of BB gelatin. Lipopolysaccharide (LPS) but not BB gelatin induced secretion of an appreciable amount of mIL-1beta. These results suggest that the activity of BB gelatin is not attributed to contamination of LPS but BB gelatin itself. It was also suggested that BB gelatin stimulated adherent PEC to newly produce and secrete cytokines.     

Apolipoprotein E genotypes of normal and hyperlipidemic subjects.

Apolipoprotein E (apo E) plays a role in the regulation of the lipid metabolism of humans. Apo E, 229 amino acid polypeptide, is classified into three major isoform (E2, E3, E4) according to the differences of amino acid in position 112 and 158. In the normal population apo E3 isoform is most prevalent and apo E2 or E4 is frequently associated with hyperlipoproteinemia. To find out the frequency of apo E isoform distribution in the Korean population, apo E genotyping was performed. After amplification of apoE gene by polymerase chain reaction (PCR), restriction isotyping was done by cleavage with restriction enzyme Hha I and polyacrylamide gel electrophoresis. The apo E allele frequency in 73 normal subjects was 4.8% for E2, 84.9% for E3 and 10.3% for E4. In diabetic patient with hyperlipoproteinemia, the frequency of apo E allele was 6.3% for E2, 81.0% for E3 and 12.7% for E4. There was no significant difference in apo E isoform distribution between diabetics and normal populations. But in patients with cardiovascular disease with hyperlipidemia, the apo E4 allele frequency was significantly higher than normal (20.0% vs 10.3%, p < 0.005). Apo E3 was the most common isoform in normal and diabetic subjects and apo E2 isoform was rather low frequency compared to Caucasians. This pattern is similar to the Japanese population but somewhat different from other populations. From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia. The PCR method may be useful in apo E genotyping.     

Retrocrural Lymph Node Metastasis Disclosed by 18F-FDG PET/CT: A Predictor of Supra-diaphragmatic Spread in Ovarian Cancer

Purpose

Retrocrural lymph nodes (RCLNs) communicate with retroperitoneal and posterior mediastinal LNs. It is possible that, when RCLNs are involved, supra-diaphragmatic extension will occur in abdomino-pelvic cancers. The authors investigated performance of ¹⁸F-FDG PET/CT to diagnose RCLN metastasis and whether RCLN metastases were associated with supra-diaphragmatic lymphatic metastases of ovarian cancer.

Materials and methods

Sixty-seven patients with stage IV ovarian cancer who had undergone ¹⁸F-FDG PET/CT were included in this retrospective study. Diagnostic performance of ¹⁸F-FDG PET/CT for RCLN metastasis was evaluated. Patients were divided into two groups by presence or absence of supra-diaphragmatic LN metastasis. The prevalences of RCLN metastasis between the two groups were compared and the odds ratio was calculated.

Results

Sensitivity and specificity of ¹⁸F-FDG PET/CT for RCLN metastasis were 96.3 and 100%, respectively. Of the 67 study subjects, 27 patients had RCLN metastases (40.3%). Fifty patients had supra-diaphragmatic LN metastases. ¹⁸F-FDG PET/CT showed 26 RCLN metastases in patients with supra-diaphragmatic LN metastases (54.5%), and only 1 in patients without supra-diaphragmatic LN metastasis (5.9%), and the difference between two groups was statistically significant (P < 0.05). The odds ratio that patients with RCLN metastasis would have supra-diaphragmatic LN metastasis was 17.3 (95% confidence interval = 2.1 to 140.9, P = 0.008).

Conclusion

Performance of ¹⁸F-FDG PET/CT to diagnose RCLN metastasis was excellent. RCLN metastasis revealed by ¹⁸F-FDG PET/CT was strongly associated with supra-diaphragmatic LN spread of ovarian cancer. Thus, RCLN metastasis could be used as a predictor of supra-diaphragmatic lymphatic metastasis of ovarian cancer.     

Prognostic Value of Metabolic Tumor Volume on 11C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma

Purpose

C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG.

Methods

A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNR_max, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNR_max, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS).

Results

Median PFS of all patients was 7.9 months (range 1.0–53.8 months). In univariate analysis, MTV (cutoff 35 cm³) was a significant prognostic factor for PFS (P = 0.01), whereas TNR_max (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03).

Conclusion

MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNR_max is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.     

Asymmetric pulsation of rat carotid artery bifurcation in three-dimension observed by ultrasound imaging

The arterial structure cyclically fluctuates in three-dimensions (3-D) caused by pulsatile blood flow. The evaluation of arterial wall motion and hemodynamics contributes to early diagnosis of carotid atherosclerosis. Ultrasound is one of the most appropriate imaging modalities to evaluate arterial wall motion in real time. Although many previous studies have discussed the mechanical properties of the carotid artery bifurcation (CAB) from the two-dimensional (2-D) view, the spatio-temporal variation of carotid artery geometry in 3-D has not yet been investigated in detail. In this study, the 3-D data set of CAB from rats was acquired using a high spatio-temporal resolution ultrasound imaging system with a 40 MHz probe using mechanical sector scanning. A total of 31 slices of cross-section images were stored and a spoke scan algorithm was implemented to radially scan the lumen area in polar coordinates based on a pre-tracked seed point. The boundary of the arterial lumen was segmented using intensity-threshold-based boundary detection and fitted by polynomial regression. Two operators, who were trained with the same protocol to minimize inter- and intra-operator variability, manually segmented the lumen boundary on systolic and diastolic phase from the gray-scale images. Finally, the 3-D lumen geometries of CAB during one cardiac cycle were constructed based on the segmented lumen boundaries. From this constructed 3-D geometry, we observed that the CAB geometry favorably expanded to the anterior/posterior direction, parallel to the sagittal plane; and the manually segmented geometry also confirmed the asymmetrical change in bifurcation geometry. This is the first study on visualization and quantification on the asymmetrical variation of the CAB geometry of a rat in 3-D during a whole cardiac cycle. This finding may be useful in understanding hemodynamic etiology of various cardiovascular diseases such as arterial stenosis and its complications, and also provides reference information for numerical simulation studies on arterial wall motion.     

Prognostic value of activated Akt expression in oral squamous cell carcinoma

BACKGROUND: Akt is a serine/threonine kinase that plays an important role in tumorigenesis and influences prognosis in several cancers. However, its importance in oral squamous cell carcinomas (OSCC) has not been elucidated. AIM: To investigate the association between the expression of activated Akt, clinicopathological factors, and E-cadherin, PCNA (proliferating cell nuclear antigen), and VEGF (vascular endothelial growth factor) expression to verify the validity of Akt as a prognostic factor in OSCC. METHODS: Phosphorylated Akt (p-Akt), E-cadherin, PCNA, and VEGF expression were assessed immunohistochemically in 84 OSCCs. The results were analysed in relation to clinicopathological factors. RESULTS: p-Akt was expressed in 29 cases. It was significantly correlated with lymph node metastasis, TNM stage, and E-cadherin expression. Univariate analysis showed that p-Akt expression, E-cadherin expression, PCNA expression, differentiation, tumour size, lymph node metastasis, TNM stage, and recurrence correlated with prognosis. Multivariate analysis showed that p-Akt expression is an independent prognostic factor in patients with OSCC. CONCLUSIONS: This study revealed that Akt activation is a significant prognostic indicator for OSCC and is correlated with E-cadherin expression. The inhibition of Akt is a possible molecular approach to the treatment of OSCC.     

The Value of SPECT/CT in Localizing Pain Site and Prediction of Treatment Response in Patients with Chronic Low Back Pain

In many circumstances, causing sites of low back pain (LBP) cannot be determined only by anatomical imaging. Combined functional and morphological imaging such as bone scan with single-photon emission computed tomography/computed tomography (SPECT/CT) may be helpful in identifying active lesions. The purpose of this study was to evaluate the usefulness of bone SPECT/CT in localizing the pain site and the treatment of chronic LBP. One hundred seventy-five patients suffering from chronic LBP who underwent SPECT/CT were included, retrospectively. All of the patients received multiple general treatments according to the symptoms, and some of them underwent additional target-specific treatment based on SPECT/CT. Numerical rating scale (NRS) pain score was used to assess the pain intensity. Of 175 patients, 127 showed good response to the given therapies, while the rest did not. Overall, 79.4% of patients with definite active lesions showed good response. Patients with mild active or no lesions on SPECT/CT had relatively lower response rate of 63.0%. Good response was observed by the treatment with the guidance of active lesions identified on SPECT/CT. SPECT/CT could be useful in identifying active lesions in patients with chronic LBP and guiding the clinicians to use adequate treatment.

Graphical Abstract

相似文献   

KSNM60 in Cardiology: Regrowth After a Long Pause

The Korean Society of Nuclear Medicine (KSNM) is celebrating its 60th anniversary in honor of the nuclear medicine professionals who have dedicated their efforts towards research, academics, and the more comprehensive clinical applications and uses of nuclear imaging modalities. Nuclear cardiology in Korea was at its prime time in the 1990s, but its growth was interrupted by a long pause. Despite the academic and practical challenges, nuclear cardiology in Korea now meets the second leap, attributed to the growth in molecular imaging tailored for many non-coronary diseases and the genuine values of nuclear myocardial perfusion imaging. In this review, we describe the trends, achievements, challenges, and perspectives of nuclear cardiology throughout the 60-year history of the KSNM.     

Prognostic implication of extrarenal metabolic tumor burden in advanced renal cell carcinoma treated with targeted therapy after nephrectomy

Objective

In the era of targeted therapy for advanced renal cell carcinoma (RCC), appropriate prognosis prediction is necessary for optimal therapy with or without cytoreductive surgery. We evaluated prognostic implication of extrarenal metabolic tumor burden in nephrectomized patients with advanced RCC.

Methods

Forty-four patients with advanced RCC who underwent ¹⁸F-fluorodeoxyglucose PET/CT were retrospectively enrolled. The patients were treated with nephrectomy and targeted therapy. On PET/CT image of each patient, maximal standardized uptake value (SUV_max) of lesions were measured, and metabolic tumor burden was measured as total lesion glycolysis (TLG) by multiplying tumor volume and mean SUV. An overall TLG was calculated as the sum of those of all lesions. The prognostic value of PET parameters (SUV_max and TLG), and established major clinical factors (serum hemoglobin and corrected calcium, and number of metastatic sites) were tested with regard to overall survival.

Results

Among 44 patients, 8 died during mean follow-up time of 21.9 ± 17.7 months. On FDG PET/CT, a total of 250 lesions were analyzed. In univariate analyses, SUV_max, TLG, number of metastatic sites, serum hemoglobin and corrected calcium were significant prognostic factors. Among them, TLG remained as an independent prognostic factor in a multivariate analysis (P = 0.038). In subgroup analyses, TLG was still a significant prognostic factor in patients treated with sunitinib only and in patients on the first staging as well as restaging.

Conclusions

Extrarenal metabolic tumor burden is a significant prognostic factor in advanced RCC patients treated with targeted therapy. In selection of candidates for cytoreductive surgery, the measurement of metabolic tumor burden may be effective.