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Purpose: To examine the effect of botulinum toxin type A (BTXA) on the formation of hypertrophic scar and to unravel its mechanism of action. Methods: HSF cells were isolated from hypertrophic scars and cultured. Immunohistochemistry (IHC) assays were performed to determine TGF-β1, FN, and Col1 expressions in hypertrophic scar and normal tissues while the expressions and phosphorylation of p38, ERK, JNK, as well as the expressions of a-SMA, Col1 and FN1 in HSF cells were evaluated by immunoblot techniques. CCK-8 and Transwell assays were used to assess the effect of BTXA on the viability and motility of HSF cells. Results: BTXA suppressed MAPK pathway in hypertrophic scar fibroblasts (p < 0.01). It also suppressed excessive collagen deposits in hypertrophic scar through MAPK pathway (p < 0.01), and restrained HSF growth and motility via MAPK pathway (p < 0.01). Conclusion: BTXA suppresses hypertrophic scarring via MAPK pathway and thus, can potentially be developed as a drug for the treatment of hypertrophic scarring. [ABSTRACT FROM AUTHOR]

Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH-1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in many different types of cancer. However, the expression of VASH-1 and its clinical value in bladder cancer remain unknown. The current study analyzed the expression of VASH-1, as well as the expression of the angiogenesis-related factors vascular endothelial growth factor-A, hypoxia inducible factor-1a and cluster of differentiation 34 in bladder cancer tissues from 50 patients using immunohistochemistry. The associations between the expression of these factors and the clinicopathological characteristics of the patients were assessed. The current study demonstrated that VASH-1 is primarily expressed in the cytoplasm of bladder cancer cells and in a fraction of vascular endothelial cells. Furthermore, the expression of VASH-1 was positively associated with the tumor stage (P<0.01), pathological grade (P<0.01) and distant metastasis (P<0.05) but not with patient age or sex (P>0.05). Spearman rank correlation tests indicated that levels of those four factors were positively correlated with each other. Kaplan-Meier analysis indicated that high expression of these four factors was significantly associated with lower 5-year overall survival and progression-free survival rates. Collectively, the results of the current study suggest that VASH-1 is clinically significant in bladder cancer and its high expression may predict the progression and prognosis of patients with bladder cancer. The present study also implies that VASH-1 may be a novel target for vascular targeting therapy. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3- gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-1β and TNF-a mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47phox translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the effect of IFN-α treatment on tumor growth and metastasis of hepatocellular carcinoma (HCC). Methods: IFN-α administration was conducted in nude mice using an orthotopic implantation model of human HCC, and the key molecular markers in the IFN-α treatment was detected by immunohistochemistry staining and PCR array. Results: Up to 12 weeks of IFN-α treatment significantly suppressed tumor growth of HCC, but relatively increased the number of circulating tumor cells, which might be due to the enhanced tumor hypoxia as well as up-regulation of metastasis-related genes, such as HIF-1α, c-met, u-PA, PDGF-A, and IL-8. However, IFN-α had no direct effect on migration and invasion of HCC cells. Conclusions: IFN-α has janus face of consistently suppressing HCC growth, however, promoting tumor metastasis capacity, which is of clinical indication for the scientific administration of IFN-α and the similar antiangiogenesis drugs for their dual effect on tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

Objective To investigate whether there is endogenous neural stem cell proliferation and whether these proliferated neural stem cells represent neural plasticity in the adult rats after cerebral infarction. Methods Cerebral infarction models of rats were established and the dynamic expression of bromodeoxyuridine (BrdU), BrdU/polysialylated neural cell adhesion molecule (PSA-NCAM) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark dividing neural stem cells. PSA-NCAM was used to mark the plasticity of neural stem cells. Results Compared with controls, the number of BrdU-positive cells in the subventricular zone (SVZ) and hippocampus increased significantly at 1st day after cerebral infarction (P < 0. 05 ), reached maximum at 7th day, decreased markedly at 14th day, but it was still elevated compared with that of the controls (P < 0.05). The number of BrdU-labeled with PSA-NCAM-positive cells increased significantly at 7th day (P < 0.05 ), reached maximum at 14th day, markedly decreased at 28th day, but it was still elevated compared with that of the controls (P < 0.05). It was equal to 60% of the number of BrdU-positive cells in the same period. Conclusion Cerebral infarction may stimulate the proliferation of endogenous neural stem cells in situ and most proliferated neural stem cells represent neural plasticity. [ABSTRACT FROM AUTHOR]

Substance P, a neuropeptide, exerts proinflammatory effects and transmits the sensation of pain. Substance P immunoreactive fibers of the synovial tissue were examined to investigate the significance of Substance P in the traumatic joint. Biopsy specimens from 15 patients (eight female and seven male) with anterior cruciate ligament (ACL) injury were examined immunohistochemically with semi-quantitative counting to correlate Substance P positive fibers of the synovial tissue with clinical data, pain intensity on a visual analog scale, and serous inflammatory indicators. The total (sum of the three compartments) expression of Substance P in females of 571.9±255.1 cm−2 was significantly greater than that of males of 241.2±126.6 cm−2. In the female group, the total number of Substance P immunoreactive fibers was significantly correlated with pain intensity ( r=0.804); in the male group, there was no significant correlation with pain intensity. The expression of Substance P in the female infrapatellar fat pad was statistically significantly correlated with pre- and postoperative erythrocyte sedimentation rate as inflammation indicators. In the male group, there was no such correlation. Substance P was well- correlated with pain and inflammatory reaction in the female joint. Neural inflammation and neural pain occur more strongly in female joints. [ABSTRACT FROM AUTHOR]

Objective To evaluate the expression of telomerase transcriptional elements-interacting factor (TEIF) in human testis under different status and its relation with human telomerase reverse transcriptase (hTERT) expression. Methods Specific antisera against TEIF were generated by immunization of rabbits with purified recombinated partial TEIF. Samples were assigned to three groups according to their pathological types, including 16 normal testes, 8 atrophic testes, and 6 testicular seminomas. They were subjected to immunohistochemical staining of TEIF and hTERT. Results from both TEIF and hTERT were analyzed semi-quantitatively and compared. Results The expressions of TEIF and hTERT were detected in all samples of normal, atrophic testes, and seminomas. No differences of TEIF expressions among these three groups were observed (P> 0.05). On the contrary, the expressions of hTERT were significantly lower in atrophic testes compared with those of normal testes and seminomas (both P < 0.05). Nevertheless, co-expressions of TEIF with hTERT were revealed to be in normal and malignant cases (P < 0.05) but not in atrophic testes, which generally presented TEIF expression. The cellular distributions of both proteins were similar and mainly in spermatocytes and some Sertoli cells, while were all negative in the interstitial cells and other stromal cells. Conclusions The uniform expressions of TEIF in all these specimens suggest that it may be a marker of testis and its related diseases. The strong expression of hTERT in normal testes and testicular seminomas comparing with the low expression in atrophic testes may suggest a role for telomerase in maintaining proliferation of germ cells. [ABSTRACT FROM AUTHOR]

Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry are those of colorectal carcinoma, but there is no associated primary colorectal carcinoma. The present study describes the case of a 53-year-old female who presented with an irritating cough and a mass around the right sternoclavicular joint. Comprehensive evaluation revealed involvement of the mediastinum, lungs, right sternoclavicular joint and right kidney. Biopsies from the mediastinal and right sternoclavicular joint tumors showed features of adenocarcinoma. Immunohistochemistry was positive for cytokeratin (CK)20 and caudal type homeobox transcription factor 2, and negative for CK7, thyroid transcription factor-1 and napsin A. Genotypic analysis identified the expression of wild-type epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine-protein kinase B-Raf and UDP-glucuronosyltransferase 1-1. There was no expression of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase and a moderate expression of excision repair cross-complementation group 1, ribonucleoside-diphosphate reductase large subunit and tubulin β-3 chain. A strong expression of thymidylate synthase and 677TC genotype expression of methylenetetrahydrofolate reductase was observed. Gastroscopy, enteroscopy, colorectal colonoscopy and positron emission tomography-computed tomography failed to find evidence of a gastrointestinal malignancy and primary lung enteric adenocarcinoma was diagnosed. The presence of multiple metastases did not permit curative surgery. The patient was treated with 3 monthly cycles of the XELOX chemotherapy regimen; the response was poor with progression of supraclavicular lesions. Treatment was switched to the TP regimen for 4 monthly cycles, which resulted in a significant reduction in the size of the lung lesions; however, the supraclavicular lesion responded poorly to the treatment. The patient then received 2 cycles of the FOLFIRI regimen; however, the lung and right supraclavicular lesions progressed, causing increased right upper limb pain. The pain was alleviated by palliative surgery. Following surgery, the DP regimen was employed. Follow-up of the patient remains ongoing. The present findings suggest that the early diagnosis and treatment of primary lung enteric adenocarcinoma is likely to improve patient outcome. [ABSTRACT FROM AUTHOR]

* Context.--Tumors harboring CIC-NUTM1 fusion are a newly recognized rare sarcoma, but the documented cases are still limited. It is unclear whether it is the same as classic CIC-DUX4 sarcoma in terms of its clinical, pathologic, and behavioral aspects. Objective.--To further explore the clinicopathologic characteristics of CIC-NUTM1 sarcoma. Design.--The cases were diagnosed based on immunophenotype, next-generation sequencing, and fluorescence in situ hybridization tests and compared with the reported CIC-NUTM1 sarcomas in the literature. Results.--Three cases of CIC-NUTM1 sarcomas involving the spine in adults were described. The tumors occurred in 2 men and 1 woman, aged 38 to 61 years. Two tumors were located in thoracic vertebrae and 1 in a cervical vertebra. All were locally advanced lesions destroying the bone and soft tissues without spinal cord involvement or metastasis. The tumors were composed of monomorphic small to medium-sized cells with round to epithelioid appearance. The architecture was lobulated and solid with diffuse or multifocal myxoid stroma. Next-generation sequencing revealed an in-frame fusion between CIC (exon 16 or 17) and NUTM1 (exon 5 or 6) in 3 cases. Fluorescence in situ hybridization confirmed CIC and NUTM1 breaks, and immunohistochemistry showed NUT staining in the nucleus. The patients died of disease 8 to 15 months (mean, 10.7 months) after presentation. Of the CIC-NUTM1 sarcomas reported in the literature along with our cases (n = 11), 8 cases developed in axial bone (5 spine, 3 skull base). Conclusions.--CIC-NUTM1 sarcomas demonstrate distinct anatomic tropism for the axial skeleton and unfavorable behavior compared with classic CIC sarcoma. [ABSTRACT FROM AUTHOR]

Background: We explore the clinical and prognostic significance of expression of vascular endothelial growth factor receptor (VEGFR)-2, platelet-derived growth factor receptor (PDGFR)-ß, and c-Met in patients with hepatocellular carcinoma (HCC). Methods: The expression of VEGFR-2, PDGFR-ß, and c-Met were determined by immunohistochemical examination of the tissues of 93 HCC patients. The relationships of these markers with clinicopathological factors and prognosis were then analyzed. Results: High expression of VEGFR-2, PDGFR-ß, and c-Met was found in 86%, 19.4%, and 80.6% of patients, respectively. Expression of VEGFR-2 correlated with gender (P = 0.044), hepatitis B surface antigen positivity (P = 0.024), degree of tumor differentiation (P = 0.023), and hepatic cirrhosis (P = 0.026). Expression of PDGFR-ß correlated with alpha-fetoprotein level (P = 0.029), tumor size (P = 0.033), and hepatic cirrhosis (P = 0.023). No significant correlations were identified between expression of c-Met and clinicopathological factors. Expression of PDGFR-ß correlated with overall survival (P = 0.046) and expression of c-Met correlated with progression-free survival (P = 0.01). Conclusions: We found that in patients with HCC, high expression of VEGFR-2 correlates with chronic hepatitis B virus infection and hepatic cirrhosis. High expression of PDGFR-ß is a predictor of poor prognosis. High expression of C-Met may predict therapeutic effectiveness of sorafenib in HCC patients. [ABSTRACT FROM AUTHOR]

B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses, and was shown to either promote or inhibit T-cell responses in various experimental systems. B7-H3 was expressed in some human cancers and correlated with poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 102 patients treated for colorectal carcinoma (CRC) by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 54.3% CRC patients, while minimal expression was found in adjacent normal colorectal tissues. Higher B7-H3 expression in tumor positively correlated with a more advanced tumor grade. In addition, consistent with a role of B7-H3 in suppressing tumor immune surveillance, the expression of B7-H3 in cancer cells negatively correlated with the intensity of tumor infiltrating T lymphocytes in both tumor nest and tumor stroma. Furthermore, we found that the level of soluble B7-H3 in sera from CRC patients was higher than healthy donors. TNF-α, an important cancer-promoting inflammatory molecule, was subsequently found to significantly increase the release of soluble B7-H3 in colon cancer cell lines. Therefore, our data suggest that both soluble and membranous B7-H3 proteins are involved in colon cancer progression and evasion of cancer immune surveillance. [ABSTRACT FROM AUTHOR]

Background: The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide. As a consequence, there is an urgent need for identifying molecular markers of HCC development and progression. Recently, several studies have suggested that the Lrig1 may have prognostic implications in various cancer types, but its clinical value in HCC is not well evaluated. Materials and methods: In this study, the expression level of Lrig1 was examined in 133 HCC tissues and adjacent normal tissues by immunohistochemistry. Furthermore, potential associations between Lrig1 expression and the carcinoma clinical parameters were investigated, including recurrence and survival rate. We silenced the Lrig1 in the normal liver cell line (LO2) and liver cancer cell line (Hep-G2) in vitro by the small interference RNA and detected its influence on proliferation, migration, and invasion. Results: The expression of Lrig1 was significantly downregulated in liver cancer tissues and cell lines, and its expression levels were related to tumor size, tumor-node-metastasis staging and tumor recurrence. Furthermore, analysis of 6-year survival of 133 HCC patients showed that those with stronger Lrig1 expression had significantly longer overall survival time than those with weaker Lrig1 expression. In addition, decreased expression of Lrig1 in vitro promoted the growth, migration, or invasion of normal liver cells and cancer cells. Conclusion: Our findings demonstrate that Lrig1 could serve as a potential marker in the prognosis of patients with HCC. We also revealed that Lrig1 might be involved in the metastatic progression of liver cancer. However, its clinical value should be further investigated in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in multiple tumors and plays an oncogenic role. OBJECTIVE: To examine the expression of AKR1B10 at mRNA and protein levels in nasopharyngeal tumors and correlate its expression with clinicopathological parameters. METHODS: A tissue microarray, paraffin blocks, and frozen surgical nasopharyngeal samples were procured. Western blot and immunohistochemistry were used to estimate AKR1B10 protein expression, and mRNA levels were detected by real time RT-PCR. RESULTS: We found that AKR1B10 expression was increased in malignant tissues compared to the normal tissues (p = 0.000). In NPC tissues, AKR1B10 expression appeared high specifically in squamous cell carcinoma, but low in basal cell carcinoma, adenoid cystic carcinoma, adenocarcinoma and undifferentiated carcinoma (p = 0.000). AKR1B10 expression also demonstrated correlation with tumor differentiation, with a high level in well and moderately differentiated but a low level in poorly differentiated carcinoma (p = 0.000). AKR1B10 was also upregulated in hyperplasia and benign tumors (p = 0.000), and demonstrated a specific nuclear distribution in these non-cancerous diseases. CONCLUSIONS: AKR1B10 is overexpressed in nasopharyngeal hyperplasia, benign tumors, and carcinomas, being a potential new biomarker. [ABSTRACT FROM AUTHOR]

Background Bmi1 has been identified as an important regulator in breast cancer, but its relationship with other signaling molecules such as ERα and HER2 is undetermined. Methods The expression of Bmi1 and its correlation with ERα, PR, Ki-67, HER2, p16 INK4a, cyclin D1 and pRB was evaluated by immunohistochemistry in a collection of 92 cases of breast cancer and statistically analyzed. Stimulation of Bmi1 expression by ERα or 17ß-estradiol (E2) was analyzed in cell lines including MCF-7, MDA-MB-231, ERα-restored MDA-MB-231 and ERα-knockdown MCF-7 cells. Luciferase reporter and chromatin immunoprecipitation assays were also performed. Results Immunostaining revealed strong correlation of Bmi1 and ERα expression status in breast cancer. Expression of Bmi1 was stimulated by 17ß-estradiol in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells, while the expression of Bmi1 did not alter expression of ERα. As expected, stimulation of Bmi1 expression could also be achieved in ERα-restored MDA-MB-231 cells, and at the same time depletion of ERα decreased expression of Bmi1. The proximal promoter region of Bmi1 was transcriptionally activated with co-transfection of ERα in luciferase assays, and the interaction of the Bmi1 promoter with ERα was confirmed by chromatin immunoprecipitation. Moreover, in breast cancer tissues activation of the ERα-coupled Bmi1 pathway generally correlated with high levels of cyclin D1, while loss of its activity resulted in aberrant expression of p16INK4aand a high Ki-67 index, which implied a more aggressive phenotype of breast cancer. Conclusions Expression of Bmi1 is influenced by ERα, and the activity of the ERα -coupled Bmi1 signature impacts p16INK4a and cyclin D1 status and thus correlates with the tumor molecular subtype and biologic behavior. This demonstrates the important role which is played by ERα-coupled Bmi1 in human breast cancer. [ABSTRACT FROM AUTHOR]

Background: Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration. However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury. In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche. We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats. Methods: The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemistry, and real-time PCR. The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay. Results: rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats. HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection. Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions. Conclusions: Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats. MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling. [ABSTRACT FROM AUTHOR]

Background: The post-translational modification of proteins, including glycosylation, differs between normal and tumor cells. The UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferases (GalNAc-Tases) family of enzymes regulates the initial steps of mucin O-glycosylation and is responsible for the altered glycosylation state observed in cancer cells. Recently it was found that GalNAc-T14 mRNA is heterogeneously expressed in breast carcinomas compared to normal tissue, however the expression profile of GalNAc-T14 protein in breast carcinomas compared to normal tissue is still unknown. In this study, we assessed the expression profile of GalNAc-T14 protein in malignant and non-malignant breast tissues by immunohistochemistry to evaluate whether GalNAc-T14 might be a potential biomarker for breast cancer. Methods: In formalin-fixed tissues, the expression level of GalNAc-T14 protein was evaluated by immunohistochemistry assay in breast tissues. Expression profiles were assessed in normal tissues, benign fibroadenomas and several types of carcinomas. Results: Our results showed that GalNAc-T14 was heterogeneously expressed in breast carcinomas compared to nonmalignant tissue. GalNAc-T14 expression was observed in 47/56 (83.9%) carcinoma samples, 7/48 (14.6%) nonmalignant breast tissue samples. GalNAc-T14 expression level was associated with histological grade. For this enzyme a significant association with invasive ductal type, mucinous adenocarcinoma and ductal carcinoma in situ (DCIS) type was found. Conclusion: Our results provide evidence that GalNAc-T14 may be a potential biomarker for breast cancer by immunohistochemistry. GalNAc-T14 expression level was associated with histological grade. GalNAc-T14 expression can provide new insights about breast cancer glycobiology. [ABSTRACT FROM AUTHOR]

To examine expression profile and prognostic significance of vascular endothelial growth factor (VEGF) and its receptors in hepatocellular carcinoma (HCC) and peritumoral tissue. Expression of VEGF-A, VEGF-C, and VEGF receptor 1(VEGFR-1), VEGFR-2, and VEGFR-3 in tumor and peritumoral liver tissue was studied by immunohistochemistry in a tissue microarray from 107 patients with HCC. Unsupervised hierarchical cluster analyses were conducted to identify relevant clusters. Staining of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 was mostly found on the tumor cells and peritumoral hepatocytes, but VEGFR-1 was mostly expressed in stromal cells. In most of the cases, the expression of VEGF-A, VEGFR-1, VEGFR-2, and VEGFR-3 in was higher in peritumoral liver tissue, while VEGF-C expression was higher in tumor. Unsupervised hierarchical clustering analysis identified four prognostically different clusters, of which cluster A was classified into the “poor prognosis group,” and the other three clusters were classified into the “good prognosis group” ( P = 0.047). Further analysis with a set of seven markers reproduced the same four cluster groups with significantly different recurrence free probability (RFP) ( P = 0.018), and the low RFP group was associated with more intrahepatic satellite lesions. Multivariate analysis showed that classification defined by seven biomarkers was of prognostic significance ( P = 0.000). Expression of VEGF and its receptors was higher in peritumoral tissue than in tumor in HCC. Seven biomarkers predicted patients’ RFP, which consisted of tumoral expression of VEGF-A, VEGFR-1, and VEGF-C as well as peritumoral expression of VEGF-A, VEGFR-1, VEGFR-2, and VEGFR-3. [ABSTRACT FROM AUTHOR]

It has been proposed that immune injury is the central mechanism of pathogenesis of the infectious disease, severe acute respiratory syndrome (SARS). To gain a better understanding of immune injury in the spleen, we investigated the number and distribution of various immune cell types in the spleens of SARS patients. We performed autopsies on six confirmed SARS cases, with six normal subjects as controls; spleen samples from these autopsies were examined with hematoxylin and eosin (H&E) sections, in situ hybridization for SARS virus genomic sequences, and immunohistochemistry with seven monoclonal antibodies to five cell types. The number and distribution of these cells were measured and analyzed using an image analysis system. SARS genomic sequences were detected in all SARS spleens. The SARS spleens all had severe damage to the white pulp and showed an alteration of the normal distribution of various cell types. Immunocytes in the red pulp were decreased by 68.0-90.7% except for CD68+ macrophages and human leukocyte antigen (HLA)-DR positive antigen-presenting cells (APC), which were decreased to a lesser degree. On average, CD68+ macrophages were increased in size by 2.21-fold. We hypothesize that the collapse of the splenic immune system plays a key role in the clinical outcome of these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: A significant percentage of confirmed severe acute respiratory syndrome (SARS) patients experienced gastrointestinal symptoms, and the viral sequence was detectable in the stool of most patients. At present, the knowledge of the pathology of the digestive system in SARS patients is limited. Because a resurgence of the SARS epidemic is constantly possible, there is an urgent need to understand the involvement of the digestive system in this new disease.METHODS: We performed seven SARS autopsies in which samples of alimentary tract and digestive glands were examined with routine pathology, electron microscopy (EM),in situhybridization (ISH), immunohistochemistry, and real-time polymerase chain reaction (PCR).RESULTS: The main histopathological finding was atrophy of the mucosal lymphoid tissue. A few mucosal epithelial cells and lymphocytes in the intestine were positively stained for coronavirus with ISH. SARS-coronavirus (CoV)-like particles were found in the mucosal epithelial cells under EM and mild focal inflammation was detected in the alimentary tract. One patient who experienced severe diarrhea had pseudomembranous enteritis of the ileum. Fatty degeneration and central lobular necrosis were observed in the liver. No evidence of direct viral infection was found in the esophagus, the stomach, the salivary gland, the liver, or the pancreas.CONCLUSIONS: In addition to the lungs, the gastrointestinal tract is another target of SARS-CoV infection, as the intestinal epithelial cells and mucosal lymphoid tissue are infected. The findings provide possible explanations for the gastrointestinal symptoms and the presence of virus in the stool of SARS patients.(Am J Gastroenterol 2005;100:169–176) [ABSTRACT FROM AUTHOR]

In this paper we tested the hypothesis that interrupting reperfusion (ischemic postconditioning) reduces the neuron death after transient global cerebral ischemia/reperfusion. Ten min transient cerebral ischemia was induced by four-vessel occlusion in male Sprague-Dawley rats. The animals underwent postconditioning consisting of 3 cycles of 15s/15s, 30s/30s or 60s/15s reperfusion/occlusion, respectively, which were applied after the start of reperfusion. Cytosolic expression of cytochrome c and caspase-3 was evaluated by immunohistochemistry. Ten min ischemia and 7 days reperfusion destroyed approximately 79% of CA1 neurons and 58% parietal cortex neurons, respectively. Three cycles of 30s/30s reperfusion/ischemia postconditioning decreased the neuron loss to 7% in CA1, and 10% in cortex. Another two postconditioning protocols failed to rescue the CA1 neuron death, but decreased the loss of cortex neurons. The expression of cytochrome c at 5h and 12h and caspase-3 at 12h increased significantly after reperfusion, which was prevented by three cycles of 30s/30s reperfusion/ischemia postconditioning. Our data provide the evidence that appropriate interrupting reperfusion is neuroprotective against global cerebral ischemia/reperfusion injury, and this protective effect is through preventing the activation of caspase and then neuronal apoptosis. [ABSTRACT FROM AUTHOR]