OBJECTIVE: To analyze the association between serum levels of S100A8/S100A9 and clinicopathological features of colorectal cancer patients.
 METHODS: A total of 82 patients with CRC and 14 healthy controls were enrolled for this study. The levels of S100A8 and S100A9 in serum were detected by ELISA assay. The association between S100A8/S100A9 and clinicopathological features was analyzed by student-t test and one-way ANOVA. Receiver Operating Characteristic curve was used to analyze diagnostic efficiency of serum S100A8 and S100A9 for colon rectal cancer. Logistic regression model was also established to analyze the possible risk factors for elevation of S100A8/S100A9.
 RESULTS: The levels of S100A8 and S100A9 were (1 403.3±593.7) and (2 890.3±994.9) pg/mL in patients with colon cancer, and (712.8±265.3) and (1 492.7±564.6) pg/mL in controls, respectively, with significant difference between the two groups (P<0.01). The similar results were found in rectal cancer patients, with a level of S100A8 and S100A9 at (1 417.7±666.5) and (3 026.7±887.6) pg/mL, respectively. Diagnostic sensitivity and specificity of S100A8 and S100A9 are better than traditional biomarkers. The levels of S100A9 in serum of CRC patients were correlated with clinical stages and distant metastasis. Serum levels of S100A9 in patients of stage III [(3 111.9±178.5) pg/mL] and stage IV [(3 831.4±278.5) pg/mL] were significantly (P<0.01) higher than that in stage I [(2 276.1±167.4) pg/mL], whereas there was significant change in S100A8 levels. Logistic regression showed the possible risk factors for the elevation of S100A9, including depth of invasion, lymphatic metastasis and degree of differentiation (P<0.05).
 CONCLUSION Serum level of S100A8 and S100A9 in CRC patients were significantly increased and serum level of S100A9 was positively correlated with the malignant features of CRC.
Calgranulin A ; Calgranulin B ; Colorectal Neoplasms ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lymphatic Metastasis ; Risk Factors

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.
Arthritis, Rheumatoid/*blood/pathology/radiography ; Arthrography ; Biological Markers/blood ; Calgranulin A/*blood ; Calgranulin B/*blood ; Humans ; Joints/pathology ; Synovial Fluid/metabolism

<b>OBJECTIVEb>To investigate the mRNA and protein expression levels of S100A8 and S100A9 in giant cell tumor (GCT) of bone, and its relation with radiological findings and biological behavior.

<b>METHODSb>Forty three patient with GCT of bone admitted in Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2009 to June 2012 were enrolled in the study. The expression levels of S100A8 and S100A9 mRNA and protein were detected by using semiquantitative RT-PCR and Western blotting in 43 specimens of GCT and 6 specimens of normal bone marrow. The CT and MRI findings of patients were retrospectively reviewed, its relation with tissue expression of S100A8 and S100A9 was analyzed.

<b>RESULTSb>Among 43 GCT cases 40 showed positive expression of S100A8 and S100A9 mRNA and protein, and the expression levels were significantly higher than those in normal bone marrow P<0.05). The expression level of S100A8 protein was significantly different in bone GCT with different composition ratio on MRI (P<0.05).The expression level of S100A9 protein was significantly different in GCT with different degree of bone destruction on CT scan (P<0.05).

<b>CONCLUSIONb>The expression of S100A8 and S100A9 mRNA and protein is up-regulated in GCT of bone. The expression of S100A8 and S100A9 is associated with the real composition ratio and the degree of bone destruction, respectively, indicating that S100A8 and S100A9 may be involved in the biological behavior of bone GCT.

Bone Neoplasms ; metabolism ; Calgranulin A ; metabolism ; Calgranulin B ; metabolism ; China ; Giant Cell Tumor of Bone ; metabolism ; Humans ; RNA, Messenger ; Tomography, X-Ray Computed ; Up-Regulation

Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.
Asthma ; Calgranulin B ; Humans ; Inflammasomes ; Inflammation ; Interleukin-18 ; Interleukins ; Myeloblastin ; Neutrophils ; Pathogen-Associated Molecular Pattern Molecules ; Phenotype ; Th17 Cells

<b>OBJECTIVEb>To investigate the expression of myeloid-related protein complex (MRP-8/14) in children with acute Kawasaki Disease (KD).

<b>METHODSb>A total of 41 children with acute KD and 40 age- and sex-matched control children with upper respiratory tract infection were recruited. Serum levels of MRP-8/MRP-14 complex were measured by ELISA, messenger ribonucleic acid (mRNA) abundance of MRP-8 and MRP-14 in circulating granulocytes and monocytes was determined by RT-PCR, and the number of circulating endothelial cells was determined by flow cytometry.

<b>RESULTSb>When the analysis was stratified according to the presence or absence of coronary artery ectasia in the KD patient group, serum levels of MRP-8/MRP-14 complex, MRP-8 and MRP-14 mRNA abundance in granulocytes, and the number of circulating endothelial cells were all significantly higher in KD patients with coronary artery ectasia than in KD patients without coronary artery ectasia (P<0.05). Serum levels of MRP-8/MRP-14 complex were positively correlated with the number of endothelial cells in the circulation (r=0.69, P<0.05).

<b>CONCLUSIONSb>Serum levels of MRP-8/MRP-14 complex are elevated in a positive association with the number of circulating endothelial cells in KD children with coronary artery ectasia, suggesting a causative role in the development of coronary artery lesions.

Acute Disease ; Calgranulin A ; blood ; genetics ; physiology ; Calgranulin B ; blood ; genetics ; physiology ; Child, Preschool ; Coronary Artery Disease ; etiology ; Endothelial Cells ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; pathology ; RNA, Messenger ; analysis

<b>BACKGROUNDb>S100A8 and S100A9 are two members of the S100 protein family characterized by the presence of two Ca2+-binding sites of the EF-hand type. Previous studies suggested that the whole S100 family displays significant functions in tumor growth, progression and invasion. This study aimed to determine the expression of the two indices of the family, S100A8 and S100A9, in lung cancer tissues and normal lung tissues and its correlation with clinical features.

<b>METHODSb>A total of 60 cases with a variety of clinical data that were diagnosed with different histological subtypes of lung cancer were investigated. Semi-quantitative reverse transcriptase-PCR (Sq-Rt-PCR) and immunohistochemical staining of cancer, adjacent and peripheral lung tissues were executed to distinguish the expression patterns of S100A8 and S100A9 and to further clarify their correlation with clinical features.

<b>RESULTSb>Immunohistochemical staining of both proteins showed a significant up-regulation in lung cancer tissue (S100A8, S100A9, P<0.0001), and PCR revealed that the levels of S100A8 and S100A9 expression were significantly higher in lung cancer tissues (S100A8 P=0.002/0.004; S100A9 P=0.022/0.026). The higher expression was found to be correlated with the clinical characteristics of adenocarcinoma, inflammation and stage IV lesion.

<b>CONCLUSIONSb>S100A8, S100A9 up-regulation was found in the lung adenocarcinoma and end stage lung cancer tissue, the correlation of which with their higher expression in inflammatory lung tissues may indicate the collaborative effect of inflammation on the progression of cancer.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Aged ; Calgranulin A ; genetics ; metabolism ; Calgranulin B ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; Inflammation ; genetics ; metabolism ; pathology ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To investigate the effect of methylation transferase inhibitor 5-aza-2'-deoxycitydine (5-aza-2 dC) on the growth, differentiation and apoptosis of human acute myeloid leukemia(AML) cell line HL-60, and to explore the possible anti-leukemia mechanism of 5-aza-2 dC. METHODS: HL-60 cells were treated by 5-aza-2 dC at various concentrations for different periods of time. The effect of 5-aza-2 dC on the growth of HL-60 cells were detected by MTT assay. The effect on the cell cycle and differentiation were detected by flow cytometry. The effect on the apoptosis were detected by Hochest33342 staining and flow cytometry. The expression of S100A8 and S100A9 was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) 5-aza-2 dC inhibited the growth of HL-60 cells in a concentration- and time-dependent manner, and HL-60 cells were arrested at G2/M phases; (2) 5-aza-2 dC enhanced the expression of cell differentiation antigen CD11b at HL-60 cells, especially at the low drug concentration; (3) 5-aza-2 dC induced HL-60 cell apoptosis in a concentration- and time-dependent manner, especially at the high drug concentration; (4) 5-aza-2 dC increased the expression levels of S100A8 and S100A9 mRNA in HL-60 cells. CONCLUSION 5-aza-2 dC can inhibit the growth of HL-60 cells accompanied with G2/M phase arrest, induce the differentiation and apoptosis of the cells, and increase the expression levels of S100A8 and S100A9 mRNA, which may be the anti-AML mechanism of 5-aza-2 dC.
Antimetabolites, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Azacitidine ; analogs & derivatives ; pharmacology ; Calgranulin A ; biosynthesis ; genetics ; Calgranulin B ; biosynthesis ; genetics ; Cell Proliferation ; drug effects ; Cell Transformation, Neoplastic ; drug effects ; Decitabine ; HL-60 Cells ; Humans ; RNA, Messenger ; biosynthesis ; genetics

BACKGROUND: S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC). METHODS: We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells. RESULTS: The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC. CONCLUSIONS: S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.
Adenocarcinoma ; Calgranulin B ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Female ; Humans ; Lung Neoplasms ; Lung ; Male ; Methods ; Neoplasm Metastasis ; Prognosis ; Smoke ; Smoking

S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F
Animals ; Bronchoalveolar Lavage Fluid ; CRISPR-Cas Systems/genetics* ; Calgranulin B ; Disease Models, Animal ; Gene Knockout Techniques ; Gene Targeting ; Lung ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin ; Phenotype

Objective To investigate the effects of paclitaxel and doxorubicin on the immune microenvironment of breast cancer in mice. Methods The CTR-DB database, a database for analysis of gene expression profiles and drug resistance characteristics related to tumor drug response, was used to analyze the effect of chemotherapeutic drugs on the immune microenvironment of breast cancer. Mouse models with breast cancer were established by in situ injection with 4T1 cells, a triple-negative breast cancer (TNBC) cells. Then they were treated with doxorubicin and paclitaxel, respectively. The sizes of tumor were recorded and analyzed by growth curve. The number of different types of immune cells was analyzed using flow cytometry. The expressions of Ki67, S100 calcium binding protein A9 (S100A9) and matrix metalloproteinase 9 (MMP9) were detected by immunohistochemistry. The cell cycles of 4T1 cells in paclitaxel group and doxorubicin group were analyzed by flow cytometry. Results The results of CTR_Microarray_75 analysis showed that the immune scores, and the number of cytotoxic lymphocytes, B lineages, CD8⁺ T cells, dendritic cells (DCs), monocytic lineages and natural killer (NK) cells in chemotherapy-sensitive breast cancer were higher than those in chemotherapy-insensitive breast cancer. Through growth curve analysis in mice with breast cancer, we found that both paclitaxel and doxorubicin could inhibit the increase of the tumor sizes, and the paclitaxel showed a higher inhibitory effect. The results of cytometry displayed that both paclitaxel and doxorubicin could restrain the expression of Ki67 and increase the number of breast cancer cells in G2/M phase, and in the paclitaxel group, the expression of Ki67 was lower and the number of breast cancer cells in G2/M phase was larger. Paclitaxel and doxorubicin enhanced the infiltration of CD45⁺ immune cells but decreased the infiltration of neutrophils. Additionally, paclitaxel promoted the infiltration of CD3⁺CD4⁺ T helper cells, CD3⁺CD8⁺ cytotoxic T cells and CD45⁺CD19⁺B cells, while doxorubicin increased the infiltration of CD4⁺CD25⁺ regulatory T cells (Tregs). The results of immunohistochemistry displayed that the paclitaxel significantly inhibited the expression of S100A9, while the doxorubicin significantly restrained the expression of MMP9. Conclusion Paclitaxel and doxorubicin can effectively inhibit the growth of breast cancer cells and change immune microenvironment of TNBC by regulating the different patterns of cell infiltration and the expression of different extracellular matrix components.
Animals ; Mice ; Humans ; Paclitaxel/pharmacology* ; Matrix Metalloproteinase 9 ; Triple Negative Breast Neoplasms/drug therapy* ; CD8-Positive T-Lymphocytes ; Ki-67 Antigen ; Doxorubicin/pharmacology* ; Calgranulin B ; Tumor Microenvironment