Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance

<p>Abstract</p> <p>Background</p> <p>Cancer invasion results from constant interactions between cancer cells and their microenvironment. Major components of the cancer microenvironment are stromal cells, infiltrating inflammatory cells, collagens, matrix metalloproteinases (MMP) and newly formed blood vessels. This study was to determine the roles of MMP-9, MMP-2, type IV collagen, infiltrating macrophages and tumor microvessels in gastric cancer (GC) invasion and their clinico-pathological significance.</p> <p>Methods</p> <p>Paraffin-embedded tissue sections from 37 GC patients were studied by Streptavidin-Peroxidase (SP) immunohistochemical technique to determine the levels of MMP-2, MMP-9, type IV collagen, macrophages infiltration and microvessel density (MVD). Different invasion patterns were delineated and their correlation with major clinico-pathological information was explored.</p> <p>Results</p> <p>MMP2 expression was higher in malignant gland compared to normal gland, especially nearby the basement membrane (BM). High densities of macrophages at the interface of cancer nests and stroma were found where BM integrity was destroyed. MMP2 expression was significantly increased in cases with recurrence and distant metastasis (<it>P = </it>0.047 and 0.048, respectively). Infiltrating macrophages were correlated with serosa invasion (<it>P </it>= 0.011) and TNM stage (<it>P </it>= 0.001). MVD was higher in type IV collagen negative group compared to type IV collagen positive group (<it>P </it>= 0.026). MVD was related to infiltrating macrophages density (<it>P </it>= 0.040). Patients with negative MMP9 expression had better overall survival (OS) compared to those with positive MMP9 expression (Median OS 44.0 vs 13.5 mo, <it>P </it>= 0.036). Median OS was significantly longer in type IV collagen positive group than negative group (Median OS 25.5 vs 10.0 mo, <it>P </it>= 0.044). The cumulative OS rate was higher in low macrophages density group than in high macrophages density group (median OS 40.5 vs 13.0 mo, <it>P </it>= 0.056). Median OS was significantly longer in low MVD group than high MVD group (median OS 39.0 vs 8.5 mo, <it>P </it>= 0.001). The difference of disease-free survival (DFS) between low MVD group and high MVD group was not statistically significant (<it>P </it>= 0.260). Four typical patterns of cancer invasion were identified based on histological study of the cancer tissue, including Washing pattern, Ameba-like pattern, Spindle pattern and Linear pattern.</p> <p>Conclusions</p> <p>Proteolytic enzymes MMP9, MMP2 and macrophages in stroma contribute to GC progression by facilitating the angiogenesis. Cancer invasion patterns may help predict GC metastasis.</p

Identification of Regional Lymph Node Involvement of Colorectal Cancer by Serum SELDI Proteomic Patterns

Background. To explore the application of serum proteomic patterns for the preoperative detection of regional lymph node involvement of colorectal cancer (CRC). Methods. Serum samples were applied to immobilized metal affinity capture ProteinChip to generate mass spectra by Surface-Enhanced Laser Desorption/ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Proteomic spectra of serum samples from 70 node-positive CRC patients and 75 age- and gender-matched node-negative CRC patients were employed as a training set, and a classification tree was generated by using Biomarker Pattern Software package. The validity of the classification tree was then challenged with a blind test set including another 65 CRC patients. Results. The software identified an average of 46 mass peaks/spectrum and 5 of the identified peaks at m/z 3,104, 3,781, 5,867, 7,970, and 9,290 were used to construct the classification tree. The classification tree separated effectively node-positive CRC patients from node-negative CRC patients, achieving a sensitivity of 94.29% and a specificity of 100.00%. The blind test challenged the model independently with a sensitivity of 91.43% a specificity of 96.67%. Conclusions. The results indicate that SELDI-TOF-MS can correctly distinguish node-positive CRC patients from node-negative ones and show great potential for preoperative screening for regional lymph node involvement of CRC

2-Phenyl-1H-1,3,7,8-tetra­azacyclo­penta­[l]phenanthrene

There are two mol­ecules in the asymmetric unit of the title compound, C19H12N4, with dihedral angles of 2.41 (10) and 10.53 (12)° between the fused ring system and the pendant phenyl ring. In the crystal, mol­ecules are linked into chains by N—H⋯N hydrogen bonds and aromatic π–π stacking inter­actions [shortest centroid–centroid distance = 3.6176 (16) Å] complete the structure

Method for Thermo-optic Analysis in a Star Sensor

An autonomous star sensor is a highly accurate attitude-measuring instrument used in spacecraft, and its performance is restricted by ambient temperature of the outer space. This paper puts forward an effective scheme to the thermooptic analysis using finite element analysis (FEA) and ray tracing in star sensor. Specific difficulties: (a) how to evaluate thermo-optic effect in star sensor, and (b) how to make FEA results useful in optical design mode have been resolved using the scheme. Based on this scheme, the errors of star sensor, which are caused by thermo-optic effects, can be investigated in any complicated temperature condition, and the required temperature scope for the thermal design can be achieved. For example, the errors of the star sensor were 0.0863" and 2.2933", when the temperature differences of the experimental optical system were 10 °C and 5 °C in axial and lateral, respectively.Defence Science Journal, 2010, 60(3), pp.276-281, DOI:http://dx.doi.org/10.14429/dsj.60.35

Expressions of toll-like receptors 2 and 4, and relative cellular factors in HIV patients with tuberculosis infection

Purpose: To investigate the expressions of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), IFN-γ (IFN- gamma), interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 10 (IL-10) in human immunodeficiency virus (HIV) patients with tuberculosis (TB) infection.Methods: Two groups of HIV patients (68 in each group) were used for this study. These were HIV with TB (HIV/TB) group and HIV without TB group. A third group (68 healthy people) served as control. Quantitative polymerase chain reaction (qPCR) was adopted to measure TLR-2 and TLR-4 expressions in peripheral blood mononuclear cells (PBMC), while the serum levels of TNF-α, IFN-γ, IL-2, IL-6 and IL-10 were determined by ELISA.Results: The △Ct values of TLR-2 and TLR-4 in HIV/TB and HIV groups were significantly lower than those in the control group (p &lt; 0.05). Compared to control group, the serum levels of TNF-α, IL-6 and IL-10 significantly increased, while IFN-γ and IL-2 in HIV/TB and HIV groups significantly decreased (p &lt; 0.05). However, IFN-γ and IL-2 decreased significantly in HIV/TB group (p &lt; 0.05). Expression of TLR2 correlated positively with serum levels of TNF-α, IL-6 and IL-10, but negatively with IFN-γ and IL-2 (p &lt; 0.05).Conclusion: TLR2 signal pathway plays a role in HIV patients with TB infection by promoting the expressions of TNF-α, IL-6 and IL-10, while inhibiting IFN-γ and IL-2 cellular factors, and thus may provide a new pathway for the treatment of patients with HIV/TB.Keywords: HIV, Tuberculosis, Toll-like receptor, Cellular factors, Tumor necrosis factor, Interleuki

Corneal stromal acupuncture combined with amniotic membrane transplantation for treating bullous keratopathy

AIM: To investigate the clinical effect for treating bullous keratopathy(BK)by anterior corneal stromal acupuncture combined with amniotic membrane transplantation.<p>METHODS: Totally 35 patients(35 eyes)with bullous keratopathy were treated by corneal stromal acupuncture combined with amniotic membrane transplantation. All patients preoperative and postoperative underwent anterior segment OCT, corneal topography, corneal sensitivity and confocal microscopy. To observe postoperative ocular symptoms in patients with BK, recurrence of bulla, changes in corneal thickness, corneal sensitivity and changes in the organizational structure of the layers of the cornea.<p>RESULTS: Thirty-five were followed up for 6-18mo. The symptom of pain disappeared in 32 cases(91%)in the first day after operation and did not recur during follow-up. The symptom of pain relieved in 3 cases(9%)in the first day after operation and disappeared in 3 days. Corneal epithelium of 9 cases(26%)were all healed within 1wk, 21 cases(60%)were all healed within 2wk, and 5 cases(14%)were all healed within 3wk. Following up for 6-18mo, there was no recurrence of symptoms or bulla. A small amount of tiny bubbles in the surrounding area appeared in 2 cases after 3 and 4wk. All patients had no neovascularization, and had smooth corneal surface. The amnions of 30 cases(86%)were thinning after 2mo, partially dissolved and absorped, not seen with the naked eye after 3mo. Thirty-four cases(97%)had no changes in vision, one case(3%)was from the light to front of the manual. After 2mo, corneal sensation decreased in 30 cases(86%), corneal thickness increased from preoperative 788±35μm to 940±43μm. After 12mo, corneal thickness increased to 1060±27μm. Results of confocal microscopy: after 3mo, the number density of the trigeminal nerve fibers under corneal basement membrane reduced, shallow stromal cells became into fibrotic stroma, deep stroma was more loose, and cells swelled significantly. The number of endothelial cells reduced and form swelled more obviously compared with preoperatively.<p>CONCLUSION: Corneal acupuncture combined with amniotic membrane transplantation can effectively control the symptoms of BK, prevent the recurrence of BK, and especially it is a simple, safe and practical way for patients with poor visual function