Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal

Although the firing activity of dopamine (DA) neurons in the ventral tegmental area (VTA) and the behavioral response to morphine rewarding properties alter as opiate withdrawal, little is known about the dynamic changes in DA signal pathway from the VTA to the nucleus accumbens (NAc) during prolonged withdrawal, and whether the changes are indicative of vulnerability to relapse of drug abuse. Here we report that morphine spontaneously withdrawn (SW) rats are incapable of responding to small dose of morphine-induced conditioned place preference (CPP) from 24h-SW to 30d-SW, but recover response at 45d-SW. Interestingly, mesoaccumbens DA signaling, including the firing of DA neurons in the VTA, contents of DA and its metabolic ratio, and the membrane level of dopamine D₁ receptor in the NAc elicited by morphine challenge, display a similar pattern of time-dependent changes during morphine withdrawal. Moreover, blockade of D₁ receptor abolishes this behavioral transition. In addition, a strong correlation was found between % change in CPP score and membrane D₁ receptor level induced by morphine challenge. These results indicate a time-dependent behavioral switch from tolerance to sensitization during the prolonged withdrawal, which could offer a window for therapeutic intervention via manipulations of D₁ receptors.     

Controlled release of stromal cell-derived factor-1α from silk fibroin-coated coils accelerates intra-aneurysmal organization and occlusion of neck remnant by recruiting endothelial progenitor cells

This study is to test the efficacy of stromal cell-derived factor-1α (SDF-1α)-coated coils together with endothelial progenitor cells (EPCs) transplantation in occluding aneurysms. Bone marrow-derived EPC surface markers were analyzed using flow cytometry. The migratory function of EPCs in response to SDF-1α was evaluated using a modified Boyden chamber assay. Capillary-like tube formation was assessed using Matrigel gel. Coil morphologies before and after coating with SDF-1α were observed under a scanning electron microscope. The level of SDF-1α in supernatants was measured by ELISA. Sprague-Dawley rats were randomly allocated into five groups. Histological analysis was performed on days 14 and 28 after coil implantation. The bone marrow-EPCs could express CD133, CD34, and VEGFR-2 and form tubule-like structures in vitro. Migratory ability of EPCs in the presence of SDF-1α-coated coils was similar to that in the presence of 5 ng/ml SDF-1α gradient. Sustained release of SDF-1α was achieved using silk fibroin as a carrier. In SDF-1α-coated coils + EPCs transplantation group, a well-organized fibrous tissue bridging the orifice of aneurysms was shown on days 14 and 28. On day 28, tissue organization was greater in the SDF-1α-coated coils group than in the unmodified coils group. Immunofluorescence showed α-smooth muscle actin-positive cells in organized tissue in sacs. Combined treatment with SDF-1α-coated coils and EPCs transplantation is a safe and effective treatment for rat aneurysms. This may provide a new strategy for endovascular therapy following aneurysmal subarachnoid hemorrhage.     

Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as R_A/C and found that the capabilities of tumor invasion and metastasis in the tumors with R_A/C < 1 were significantly higher than those with R_A/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with R_A/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with R_A/C < 1 and ALDH1A1^high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that R_A/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC.     

A case of blastic plasmacytoid dendritic cell neoplasm with ecchymotic lesions on the whole body

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as “eczema”. The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months.     

Overexpression of GEFT,a Rho family guanine nucleotide exchange factor,predicts poor prognosis in patients with rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is one of the most common soft-tissue sarcomas in children and adolescents with poor prognosis. Yet, there is lack of effective prognostic biomarkers for RMS. The present study, therefore, aimed to explore potential biomarkers for RMS based on our previous findings using array comparative genomic hybridization. We investigated guanine nucleotide exchange factor, GEFT, at expression level in 45 RMS patients and 36 normal striated muscle controls using immunohistochemistry using tissue microarrays. The expression rate of GEFT in RMS samples (42/45, 93.33%) was significantly higher (P<0.05) than that in normal controls (5/36, 13.89%). Moreover, the overexpression rate of GEFT in RMS (31/45, 68.89%) was also significantly higher (P<0.05) than that in normal controls (0/36, 0.00%). Increased expression of GEFT correlated significantly with advanced disease stages (stages III/IV) (P=0.001), lymph node metastasis (P=0.019), and distant metastasis (P=0.004), respectively, in RMS patients. In addition, RMS patients having overexpressed GEFT experienced worse overall survival (OS) than those having low levels of GEFT (P=0.001). GEFT overexpression was determined to be an independent prognostic factor for poor OS in RMS patients (hazard ratio: 3.491, 95% confidence interval: 1.121-10.871, P=0.004). In conclusion, these observations provide the first evidence of GEFT overexpression in RMS and its correlations with disease aggressiveness and metastasis. These findings suggest that GEFT may serve as a promising biomarker predicting poor prognosis in RMS patients, thus implying its potential as a therapeutic target.     

Elevated cleaved caspase-3 is associated with shortened overall survival in several cancer types

Emerging evidence has indicated that apoptotic cells have a compensatory effect on the proliferation of neighboring cells. Recent studies have shown that apoptotic tumor cells stimulate the repopulation of tumors from a small number of surviving cells by cleaved caspase-3 regulation and elevated tumor cleaved (and thus activated) caspase-3 expression levels predict worse treatment outcomes in cancer patients. The prognostic significance of cleaved caspase-3 should be demonstrated in more human cancer types and larger subjects. Here, we examined the cleaved caspase-3 expression in 367 human tumor samples (gastric cancer: 97 cases, ovarian cancer: 65 cases, cervical cancer: 104 cases; colorectal cancer: 101 cases) with immunohistochemistry (IHC) and the relationship between the expression of cleaved caspase-3 and various clinicopathological factors were also detected. We found that, cleaved caspase-3 was significantly associated with pathological risk factors (P < 0.005) for the studied cancers, such as tumor stage, lymph-node metastasis, differentiation and so on. In univariate and multivariate analysis, patients with high expression of cleaved caspase-3 had a significant shorter overall survival time compared with those with low cleaved caspase-3 expression in gastric cancer (P < 0.001), ovarian cancer (P < 0.001), cervical cancer (P = 0.002), colorectal cancer (P < 0.001) individually and in the patients combined (P < 0.001). Cox regression results suggested cleaved caspase-3 as an independent prognosis predictor for the studied four cancer types. Our study showed cleaved caspase-3 was well correlated to progression, aggressive behaviors in the studied cancer, and implicated it as a potential predictive factor for the prognosis of the four cancer types. It also indicated cleaved caspase-3 as a potential therapeutic target for cancer patients.     

SF6 abatement in a packed bed plasma reactor: study towards the effect of O2 concentration

SF₆ is a greenhouse gas with extremely high global warming potential value (GWP). In this paper, oxygen and a packed bed plasma reactor (PBR) were applied to remove it. The synergistic effect between oxygen and PBRs was evaluated by the destruction and removal efficiency (DRE) and energy yield (EY) at different oxygen concentrations. The results show that excessive oxygen weakened the micro-discharge in a PBR to suppress SF₆ degradation while the addition of a proper amount of oxygen (1–4%) can improve the DRE and EY. 2% O₂ in the system had the best promoting effect on the destruction of 6–10% SF₆, which made the maximum energy yield (EY) increase by 50.99% to 37.99 g kW⁻¹ h⁻¹ (SF₆ concentration was 10%, flow rate was 150 mL min⁻¹). Moreover, in the flow rate range of 100 mL min⁻¹ to 250 mL min⁻¹, the DRE decreased and the EY increased with the flow rate. In addition, the selectivity of different products were affected by the oxygen concentration. For 6% SF₆, SO₂F₂ selectivity was always the highest while SO₂ was always the lowest; when the oxygen concentration did not exceed 2%, SOF₂ selectivity was higher than SOF₄, otherwise, SOF₄ selectivity was higher than SOF₂. This paper provided experimental support for better understanding of the effect of additional gas concentration on SF₆ decomposition in a PBR.

SF₆ is a greenhouse gas with extremely high global warming potential (GWP).     

Surgical management of Squamous Cell Carcinoma of the lower lip: An experience of 109 cases

Objectives: We are presenting our experience collected from a series of 109 cases with SCC of the lower lip focusing on clinical features of patients and surgical approach. Study Design: We retrospectively analyzed medical records of patients diagnosed with Squamous Cell Carcinoma (SCC) of the lower lip at the Oral and Maxillofacial surgery at Xi’an Jiaotong University during a period between 1999 and 2008. Results: A total of 109 patients with lip cancer were included in the study. When no frozen-section test was performed, the neoplasia was removed with a margin of at least 6 mm. Different surgical techniques were used for lip reconstruction after tumor excision. Neck dissection was performed in all patients with clinically palpable lymph nodes. Median follow-up was 38 months. During follow-up, recurrence occurred in 5 patients, 3 patients developed neck metastases, distant metastases developed in 1 patient. Five patients died during observation period. Conclusions: The patient-related and defect-related issues must be taken into consideration during reconstruction for surgical defect. For N0 patients, we recommend wait-and-see policy. Early detection, careful follow-up and prompt neck is essential for the successful treatment. Key words:Lip cancer, surgical management, reconstruction.