Receptor for advanced glycation end-products (RAGE) mediates phagocytosis in nonprofessional phagocytes.

In mammals, both professional phagocytes and nonprofessional phagocytes (NPPs) can perform phagocytosis. However, limited targets are phagocytosed by NPPs, and thus, the mechanism remains unclear. We find that spores of the yeast Saccharomyces cerevisiae are internalized efficiently by NPPs. Analyses of this phenomenon reveals that RNA fragments derived from cytosolic RNA species are attached to the spore wall, and these fragments serve as ligands to induce spore internalization. Furthermore, we show that a multiligand receptor, RAGE (receptor for advanced glycation end-products), mediates phagocytosis in NPPs. RAGE-mediated phagocytosis is not uniquely induced by spores but is an intrinsic mechanism by which NPPs internalize macromolecules containing RAGE ligands. In fact, artificial particles labeled with polynucleotides, HMGB1, or histone (but not bovine serum albumin) are internalized in NPPs. Our findings provide insight into the molecular basis of phagocytosis by NPPs, a process by which a variety of macromolecules are targeted for internalization.

Concurrent paclitaxel-based chemo-radiotherapy for post-surgical microscopic residual tumor at the bronchial margin (R1 resection) in non-small-cell lung cancer.

BACKGROUND: The microscopic residual tumor at the bronchial margin after radical surgery (R1 resection) affects prognosis negatively in non-small-cell lung cancer (NSCLC) patients. For patients with good performance status, a potential cure still exists. Here, we report the outcomes of concurrent paclitaxel-based chemo-radiotherapy (CRT) for NSCLC patients with microscopically positive bronchial margins or peribronchial infiltration. METHODS: A retrospective search in the clinical database was conducted in three hospitals. Patients were identified and evaluated if treated with radiotherapy combined with paclitaxel-based chemotherapy. The objects analyzed were local control time, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. RESULTS: Sixty-one patients with microscopic residual tumor at the bronchial stump following pulmonary lobectomy were identified. Forty-six patients who had received concurrent paclitaxel-based CRT were analyzed. The median follow-up was 40 months (range: 15.0-77.5 months). The 1-, 2- and 3-year survival rates were 97.8%, 60.9% and 36.9%, respectively. The local recurrences were recorded in 19.6% (9/46) patients. Median PFS and OS for the evaluated cohort were 23.0 [95% confidence interval (CI): 21.3-24.7] and 32.0 (95% CI: 23.7-40.3) months, respectively. The most common side effects were hematological toxicity (neutropenia, 93.5%; anemia, 89.1%; and thrombocytopenia, 89.1%) and no treatment-related deaths. Grade ≥2 acute radiation-induced pneumonitis and esophagitis were recorded in 43.5% (20/46) and 26.1% (12/46) patients, respectively. By univariate analysis, non-squamous cell lung cancer was associated with a significantly longer survival time (45.1 vs 26.4 months, p = 0.013). CONCLUSIONS: For NSCLC patients with post-surgical microscopic residual tumor at the bronchial stump, concurrent paclitaxel-based chemo-radiotherapy achieved promising outcomes with accepted treatment-related toxicity.

Stereotactic body radiation therapy for post-pulmonary lobectomy isolated lung metastasis of thoracic tumor: survival and side effects.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has emerged as an alternative treatment for patients with early stage non-small cell lung cancer (NSCLC) or metastatic pulmonary tumors. However, for isolated lung metastasis (ILM) of thoracic malignances after pulmonary lobectomy, reported outcomes of SBRT have been limited. This study evaluates the role of SBRT in the treatment of such patients. METHODS: A retrospective search of the SBRT database was conducted in three hospitals. The parameters analyzed in the treated patients were local control, progression-free survival (PFS), overall survival (OS), and the treatment-related side-effects. RESULTS: In total, 23 patients with single ILM after pulmonary lobectomy treated with SBRT were identified and the median follow-up time was 14 months (range: 6.0-47.0 months). Local recurrences were observed in two patients during follow-up and the 1-year local control rate was 91.3%. Median PFS and OS for the studied cohort were 10.0 months [95% confidence interval (CI) 5.1-14.9 months] and 21.0 months (95% CI 11.4-30.6 months), respectively. Acute radiation pneumonitis (RP) of grade 2 or worse was observed in five (21.7%) and three (13.0%) patients, respectively. Other treatment-related toxicities included chest wall pain in one patient (4.3%) and acute esophagitis in two patients (8.7%). By Pearson correlation analysis, the planning target volume (PTV) volume and the volume of the ipsilateral lung exposed to a minimum dose of 5 Gy (IpV5) were significantly related to the acute RP of grade 2 or worse in present study (p < 0.05). The optimal thresholds of the PTV and IpV5 to predict RP of acute grade 2 or worse RP were 59 cm3 and 51% respectively, according to the receiver-operating characteristics curve analysis, with sensitivity/specificity of 75.0%/80.0% and 62.5%/80.0%. CONCLUSIONS: SBRT for post-lobectomy ILM was effective and well tolerated. The major reason for disease progression was distant failure but not local recurrence. The PTV and IpV5 are potential predictors of acute RP of grade 2 or higher and should be considered in treatment planning for such patients.

Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model.

The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7-124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2-62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14-47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice.

Systematic evaluation on the use of acellular dermis matrix graft in prevention Frey syndrome after parotid neoplasm surgery.

OBJECTIVE: To study the effectiveness and safety of acellular dermal matrix (ADM) graft in preventing Frey syndrome after parotid neoplasm surgery, we reviewed foreign reported clinical randomized controlled trials systematically. Based on this review, we aimed to assess the effectiveness of ADM graft and provide reliable evidence for clinical application. METHODS: We reviewed foreign-language databases, such as MEDLINE, applied meta-analysis with Rev.Man 5, and drew forest plots with odds ratio as effect size. RESULTS: Three trials were recruited. The morbidity of Frey syndrome in experimental group was significantly lower than that in control on both subjective index and objective index, with odds ratios at 0.03 (95% confidence interval, 0.01-0.11) and 0.03 (95% confidence interval, 0.01-0.12), respectively. There was no significant difference between ADM group and blank control in total adverse reactions and complication incidence, whereas results differed for a kind of specific adverse reaction or complication. CONCLUSIONS: Based on existing research data, implanting ADM could effectively prevent Frey syndrome, and its poor prognosis effects did not significantly increase, which suggested that its total safety was reliable. Nevertheless, further investigations about the difference on a specific adverse reaction or complication were still needed.

Angiopoietin-2 expression is correlated with angiogenesis and overall survival in oral squamous cell carcinoma.

This study sought to determine the expression of angiopoietin-2 (Ang-2) and vascular endothelial cell growth factor (VEGF) in oral squamous cell carcinoma (OSCC) and assess their correlations with tumor progression, angiogenesis, vessel maturation, and clinical survival. Tumor tissue from 102 OSCC patients, adjacent noncancerous oral tissue from 79 OSCC patients, and normal oral mucosa from 35 control patients were examined for Ang-2 and VEGF expression using conventional immunohistochemistry. Microvessel density (MVD) and vessel maturation index (VMI) were assessed by double-label immunohistochemistry staining using anti-CD34 and anti-alpha-smooth muscle actin, respectively. Although the proportion of OSCC samples positive for Ang-2 or VEGF expression was significantly higher than that observed in the adjacent noncancerous tissue and normal oral mucosa (P < 0.001), neither Ang-2 nor VEGF expression was associated with the clinicopathological parameters analyzed in OSCC patients. However, MVD and VMI were significantly associated with the expression of Ang-2 (P = 0.001 and P = 0.014, respectively); VEGF expression was associated MVD (P = 0.004). The MVD of OSCC tissues expressing both Ang-2 and VEGF was significantly higher than observed in the double-negative samples (P < 0.05). Multivariate regression and Kaplan-Meier analyses revealed that Ang-2 was negatively associated with the overall survival of OSCC patients. Expression of Ang-2 was associated with angiogenesis and vessel maturation in OSCC. Further studies will evaluate the prognostic value of determining Ang-2 expression in OSCC.

Comparison of 64-slice CT perfusion imaging with contrast-enhanced CT for evaluating the target volume for three-dimensional conformal radiotherapy in the rabbit VX2 brain tumor model.

CT perfusion imaging is a promising technique for delineating the target volume for three-dimensional conformal radiotherapy, but it is difficult in humans to obtain gross pathological samples at the same level of the brain tumor to evaluate this technique. The aim of this study was to use the BV map of CT perfusion imaging to assess the target volume in the rabbit VX2 brain tumor model, which has similar characteristics to human brain tumor, and compare the results to those of CECT. New Zealand white rabbits were used for the animal model. After tumor cell implantation 21 rabbits underwent 64-slice CT scanning. The target slice was selected and the maximum major axis length and minimum minor axis length of the tumor in the target slice on BV maps and contrast-enhanced CT images were measured. Pathological specimens were obtained from the rabbit brains which were removed intact. The GTV and CTV of the imaging methods were compared. Scanning was successful in 20 rabbits. The CECT images showed the target area for the VX2 tumor in 16 rabbits. The BV maps showed the target area for the tumor in 20 rabbits. The probability was 95% that the GTV determined by pathology can be covered completely when BV maps are used. CT perfusion imaging appears to be a promising technique for delineating the GTV of brain tumors in clinical practice.

[Non-small cell lung cancer evaluated by first pass dynamic contrast-enhanced 16-slice spiral CT: correlation of tumor vascularity with pathological characteristics].

OBJECTIVE: To investigate the role of first pass dynamic 16-slice spiral computed tomography in the evaluation of tumor angiogenesis in patients with non-small cell lung cancer (NSCLC) and to assess its importance in predicting pathologic characteristics. METHODS: The first pass dynamic 16-slice spiral computed tomography was performed in 33 patients with NSCLC. Their peak heights (PH) were measured with dynamic evaluation software. Their angiogenesis were labelled by anti-CD34 monoclonal antibody. The first pass peak heights (PH) in 33 patients with NSCLC were compared with their microvessel densities (MVD) and their relationships were assessed by linear regression analysis. RESULTS: Among the 33 patients with NSCLCs, the mean first pass PH and MVD of N1-2 were significantly higher than those at stage No (P < 0.01). The first pass PH of 33 NSCLC was correlated positively with MVDs. To differentiate stage N0 from stage N1-2 with 12 HU cutoff value of the first pass PH, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.0%, 75.0%, 84.8%, 91.7% and 66.7%, respectively. CONCLUSION: The first pass dynamic contrast enhanced CT may be a predictor of tumor angiogenesis in patients with NSCLC and its pathologic characteristics, and may be helpful to improve the accuracy of lymph node staging with conventional CT.

[Prognostic value of 9mTc-HL91 SPECT hypoxia imaging in patients with advanced NSCLC].

OBJECTIVE: Tumor hypoxia can influence response to radiotherapy and other treatment modalities. Oxygenation status is proved to be an independent prognostic factor. 99mTc-HL91 (99mTc labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) is a potential noninvasive marker of tumor hypoxia. It has been reported that 99mTc-HL91 has certain validity for hypoxia imaging. But its clinical study had not been reported widely. This study was carried out to evaluate the relationship between the T/N ratio of HL91 SPECT hypoxia imaging and the radiotherapeutic outcome. METHODS: 32 patients with pathologically proven non-small cell lung cancer received three-dimensional conformal radiotherapy were enrolled into the study. 99mTc-HL91 SPECT scanning was performed in all patients at one or two days before radiotherapy. It was also performed in 18 patients at one or two days after the onset of radiotherapy, when they received a dose of 30 - 40 Gy already. Anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively, after intravenous injection of approximately 740 MBq 99mTc-HL91. Regions of interest (ROIs) were drawn in the tumor and the contralateral normal lung tissue, and the radioactivity ratio of tumor to normal tissue (T/N) was calculated. To assess whether the tumor uptake of 99mTc-HL91 is predictive of treatment response, the SPECT results were correlated with the results of clinical follow-up. RESULTS: The relationship between T/N ratios at 4 h images after injection was shown to be the best of three acquired images before radiotherapy. The response and overall survival to radiotherapy were analyzed for all 32 patients. The results of 9mTc-HL91 correlated well with radiotherapy response (P = 0. 002) and also patients' survival (P = 0.043). The average T/N values of 18 patients who received serial scanning were 1.57 +/- 0.18, 1.44 +/- 0.19 and 1.30 +/- 0.14, respectively. There was a significant difference between those three groups (P = 0. 000). The T/N changes during radiotherapy were not associated with the treatment outcome. CONCLUSION: HL91 SPECT imaging can identify the hypoxia status and changes during radiotherapy in lung cancer. Hypoxia SPECT imaging with HL91 before treatment may predict radiotherapy response and patients' survival. Longer follow up in more patients is planned to confirm this result.

[Hippocampal formations, amygdala and anterior temporal lobes: normative volumetric measurements from MR imaging in normal adults of China].

OBJECTIVE: To define the normal range of volumetric values of hippocampal formations (HPF), amygdala (AM) and anterior temporal lobes (ATL). METHODS: One hundred and two Chinese normal adults underwent MRI scan on oblique coronal section. Volumes of the anterior temporal lobes, hippocampal formations and amygdala were obtained on T1WI. The mean values and the range of 95% normal values were obtained by statistical data processing and analysis. RESULTS: The mean values of standardized volumes of anterior temporal lobes in the subjects aged 20 yr.-, 40 yr.- and > or = 60 yr. were: 59.07 +/- 2.02 cm3, 55.55 +/- 2.23 cm3, 52.88 +/- 2.07 cm3 (Right); 57.25 +/- 2.15 cm3, 53.23 +/- 1.72 cm3, 51.63 +/- 2.18 cm3 (Left); and of amygdala in those aged 20 yr.-, 40 yr.- and > or = 60 yr. were: 1.54 +/- 0.09 cm3, 1.38 +/- 0.08 cm3, 1.29 +/- 0.09 cm3 (R); 1.37 +/- 0.09 cm3, 1.29 +/- 0.08 cm3, 1.23 +/- 0.09 cm3(L). The 95% normal values of HPF in the subjects aged 20 yr.- ranged from 2.52 to 3.11 cm3(R), and from 2.40 to 2.98 cm3(L); in those aged > or = 60 yr. ranged from 2.33 to 2.65 cm3 (R) and from 1.98 to 2.64 cm3(L). There was no significant difference in the volumes of hippocampal formations between two groups under 60 yr.. And a decrease of the volumes of hippocampal formations could been seen in the > or = 60 yr. group. No significant difference in the volumes of hippocampal formations, amygdala and anterior temporal lobes was seen in the sex groups and handedness groups. CONCLUSION: The data on standardized volumes of HPF, AM, ATL in this study can serve as a foundation on which to provide normal index and useful guidelines for reference in early diagnosis and treatment of Alzheimer's disease and temporal lobe epilepsy.