[Analysis for the breast cancer screening among urban population in Hebei province, 2018-2019].

From 2018 to 2019, 3 453 cases of high-risk population were screened by the Cancer Screening Program in Urban China (CanSPUC) in Hebei Province, with the age of (53.94±8.00). 147 and 686 cases of breast cancer positive and suspicious positive patients were found, with the positive rate and suspicious positive rate of 4.26% and 19.87% respectively. The suspicious positive rate of 45-49 years old age group was the highest (28.32%), and the positive rate of over 70 years old age group was the highest (7.32%). The positive detection rate of mammography combined with ultrasound was 5.16%, which was higher than that of ultrasound alone (2.46%) (χ²=30.28,P<0.001) or mammography alone (3.06%) (χ²=14.56,P<0.001).

[Expression of DNA mismatch repair protein in endometrial carcinomas and its correlation with clinicopathologic features].

OBJECTIVE: To study the expression of mismatch repair protein in a series of endometrial carcinomas and its correlation with clinicopathologic features. METHODS: The clinical data of 150 consecutive cases of endometrial carcinoma were collected during the period from December, 2014 to August, 2015 in Fudan University Cancer Center. Morphologic features including tumor infiltrating lymphocytes (TIL), peritumoral lymphocytes and tumor heterogeneity were reviewed. Immunohistochemistry for expression of mismatch repair proteins was performed. The correlation with clinicopathologic features was analyzed. RESULTS: Loss of mismatch repair protein expression was observed in 43 cases (28.7%), including loss of MLH1/PMS2 in 27 cases (18%), loss of MSH2/MSH6 in 7 cases (4.7%), loss of MSH6 in 6 cases (4%) and loss of PMS2 in 3 cases (2%). There were 23.3% and 27.1% of mismatch repair protein-deficient endometrial carcinomas in women under and above 50 years of age, respectively, which was not statistically significant. Amongst the 12 cases with family history of tumors, 4 of the 6 mismatch repair protein-deficient cases were under 50 years of age, which was higher than that in the 6 cases with mismatch repair protein expression (P=0.014). The mismatch repair protein-deficient group showed significantly more prominent TIL and peritumoral lymphocytes than protein-expression group (P=0.033 and <0.001). Moreover, there were also significant differences in depth of myometrial invasion and occurrence of synchronous malignancy (2 cases of ovarian clear cell carcinoma and 1 case of colonic carcinoma) between the two groups (P=0.039 and 0.022). However, there were no significant differences in lymph node metastasis, tumor heterogeneity, lower uterine segment involvement and tumor stage between the two groups. CONCLUSIONS: Prominent TIL and peritumoral lymphocytes characteristically occur in mismatch repair protein-deficient endometrial carcinomas. Patient age does not significantly correlate with the loss of mismatch repair protein expression, but individuals under 50 years of age are more likely to have no expression if there is family history of tumors.

Mechanism of the high coagulation state of breast cancer tissue factor.

OBJECTIVE: We conducted this study to analyze the mechanism behind the high coagulation state induced by circulating plasma microparticle tissue factor (MP-TF) in patients with breast cancer. PATIENTS AND METHODS: 87 cases of breast cancer patients (10 cases of TNM stage I, 16 cases of II, 32 cases of III, 29 cases of IV; 8 cases of pathological type in situ carcinoma, 15 cases of ductal carcinoma, 64 cases of invasive cancer) were used as the observation group and 20 cases of benign breast lesions were used as the control group to compare MP-TF levels of plasma and coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer body (D-D) level and NF-κB signaling pathway index including P50, p65, TAK1 and IκBα levels. RESULTS: The plasma MP-TF level in the observation group was significantly higher than that in control group, and the level of MP-TF in the observation group increased with an increase in depth of TNM stage and tumor invasion; differences were statistically significant (p<0.05). In the observation group, the plasma PT and APTT were shortened, and the levels of FIB and D-D were increased; the differences were statistically significant (p<0.05). In the observation group, the levels of P50, p65, TAK1, IκBαin circulating blood were higher than those in control group; the differences were statistically significant (p<0.05). After the Pearson test, the plasma levels of MP-TF in patients with breast cancer were negatively correlated with PT and APTT, and positively correlated with FIB, D-D values and the levels of p50, p65, TAK1 and IκBα (4 p<0.05). CONCLUSIONS: MP-TF can lead to high blood coagulation in patients with breast cancer through the activation of NF-κB signaling pathway, which may become a new target for the intervention of the disease.

Chronic alcohol administration affects purine nucleotide catabolism in vivo.

AIMS: To investigate the relationship between chronic alcohol administration and purine nucleotide metabolism in vivo. MAIN METHODS: Rat models of alcohol dependence and withdrawal were used. The concentrations of uric acid (UAC), urea nitrogen (UREA), creatinine (CREA), and beta-2-microglobulin (ß2-M) and creatinine clearance rate (CCR) in plasma were measured. The PLC method was used to detect the absolute content of purine nucleotides in different tissues. Enzymatic activities of adenosine deaminase (ADA), xanthine oxidase (XO), ribose 5-phosphate pyrophosphokinase (RPPPK), glutamine phosphoribosylpyrophosphate amidotransferase (GPRPPAT), hypoxanthine-guanine phosphate ribose transferase (HGPRT), and adenine phosphoribosyltransferase (APRT) in the tissues were analyzed. Real-time PCR was used to determine the relative level of ADA and XO. KEY FINDINGS: The renal function of rats with alcohol dependence was normal. Further, the content of purine nucleotides (GMP, AMP, GTP, and ATP) in tissues of the rats was decreased, which indicated that the increased uric acid should be derived from the decomposition of nucleotides in vivo. The activity of XO and ADA increased, and their mRNA expression was enhanced in the alcohol dependence group, but there was no significant difference in the activity of RPPPK and GPRPPAT in the liver, small intestine, and muscle; furthermore, no significant difference in the activity of HGPRT and APRT was observed in the brain. SIGNIFICANCE: These results indicate that chronic alcohol administration might enhance the catabolism of purine nucleotides in tissues by inducing gene expression of ADA and XO, leading to elevation of plasma uric acid levels.

Effect of cholecystokinin on cytokines during endotoxic shock in rats.

AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8mg.kg(-1),iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8mg.kg(-1)); CCK-8 (40 micro.kg(-1), iv) or normal saline (control) groups. Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were assayed with ELISA kits. RESULTS: CCK-8 reversed LPS-induced decrease of mean artery blood pressure (MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 +/- 687 ng.L(-1) vs 128 +/- 22 ng.L(-1), P<0.01), while contents of TNF-alpha and IL-1beta elevated significantly (277 +/- 86 ng.L(-1) vs not detectable and 43 +/- 9 ng.L(-1) vsnot detectable, P<0.01) but less extent than IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF-alpha IL-1beta and IL-6. LPS elevated spleen and lung content of IL-1beta significantly (5184 +/- 85 ng.L(-1) vs 1047 +/- 21 ng.L(-1) and 4050 +/- 614 ng.L(-1) vs not detectable, P<0.01), while levels of TNF-alpha and IL-6 also rose significantly but in less extent than IL-1beta. CCK-8 inhibited the LPS-induced increase of the cytokines in spleen and lung. In the heart, CCK-8 significantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L(-1) in CCK-8+LPS group vs 1599 +/- 227 ng.L(-1) in LPS group, P < 0.01), and IL-1beta (282 +/- 93 ng.L(-1) in CCK-8+LPS group vs 621 +/- 145ng.L(-1) in LPS group, P < 0.01). CONCLUSION: CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.

[Human T cell and monocyte modulating activity of Rhizoma typhonii in vitro].

OBJECTIVE: To study the immunological modulating activity of Rhizoma typhonii (RT) on lymphocytes in vitro. METHODS: Effect of RT extract (RTE) on mice spleen cells and human lymphocytes proliferation was detected by sheep erythrocytes rosette forming test after lymphocytes had been isolated and purified. The activity of human killer cells and natrral killer (NK) cells was tested using 51 Cr free test. The production of cytokine of macrophages was examined using ELISA test and biological test and the phagocytic function of macrophage on tumor cell was determined using 3H incorporation assay. The chemical ingredients of RT were analyzed using chromatography and the molecular weight of their active principle was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis technique (SDS-PAGE) method. RESULTS: RTE could markedly stimulate the mice spleen cells and human lymphocytes to proliferate in a dose-effect dependent manner; the effector cell of RTE is T cells. RTE enhanced human killer cell, the allo-antigen specific cytotoxic T lymphocytes (CTL) activity and the nonspecific activity of NK cells. Furthermore, RTE stimulated macrophage to produce tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1), and enhanced phagocytic activity of macrophage to tumor cells. The elution of RTE from chromatography showed that the active principle of RT was glycoproteins in nature and had an apparent molecular weight of 66 kDa. CONCLUSION: RTE has immunoenhancing activity to human T cell and macrophage, through stimulating the killer cell and phagocytosis of tumor cell and allo-antigen, which could be used clinically for modulating immune responses and for treating tumor and other diseases.

[Immunomodulatory activity and anti-tumor activity of Oldenlandia diffusa in vitro].

OBJECTIVE: To study the effect of Oldenlandia diffusa (OD) on lymphocytes and tumor cells in vitro. METHODS: Effects of OD extract (ODE) on proliferation of spleen cells of mice and the phagocytosis of monocytes to tumor cells using 3H incorporation were analysed, and effect on specific activity of natural killer (NK) cells to human and mice's tumor cells was determined using free 51 Cr experiments, effects on B cells' antibody production and cytokine of monocyte production were investigated by ELISA and biological method, the chemical composition of OD was analyzed by chromatography, protease digestion and sugar decomposition (NaIO4) test. RESULTS: ODE could vigorously promote the proliferative activity of spleen cells in mice, specific lethal activity of human and mice's NK cell to tumor cells, B cells' antibody production, monocytes' cytokine production and its phagocytosis to remove the tumor cells. By means of chromatography, protease E digestion and NaIO4 treatment, the result of chemical composition analysis showed that the component of OD was 90 kDa glycoprotein. CONCLUSION: ODE has immuno-modulating activity and anti-tumor activity in vitro through stimulating the immune system to kill or engulf tumor cells, which could be used clinically for immune function modulation and to treat tumor and other diseases.

Correlation between MTA2 overexpression and tumour progression in esophageal squamous cell carcinoma.

The aim of this study was to clarify the clinicopathological outcome and prognostic significance of metastasis-associated gene 2 (MTA2) in esophageal squamous cell carcinoma (ESCC). Immunohistochemical staining for MTA2 was performed on surgical specimens obtained from 162 patients with ESCC. Relationships between MTA2 expression and clinicopathological factors, including prognosis, were analyzed. Significant correlations were noted among MTA2 overexpression and TNM clinical classification staging, depth of invasion, presence of regional lymph node metastasis, presence of distant metastasis, lymphatic invasion, blood-vessel invasion and the 5-year survival rates. The expression of MTA2 protein was correlated with tumour progression. Patients with MTA2 overexpression tended to have poor prognosis compared to patients with MTA2 underexpression.

Immunomodulating activity of seaweed extract on human lymphocytes in vitro.

Effect of eight kinds of seaweed extract (SWE) on human lymphocytes was studied in vitro. The extracts of Hizikiafusiformis and Meristotheca papulosa (green) markedly stimulated human lymphocytes to proliferate, whereas Eucheuma muricatum and Meristotheca papulosa (red) weakly stimulated proliferation. The responder cells are T cells, because T cells purified by sheep red blood cell (SRBC) rosette-formation were significantly stimulated with SWE, but B cells were not. These extracts enhanced the induction of cytotoxic T lymphocyte (CTL) activity, but failed to enhance natural killer (NK) cell activity. These extracts had a stimulatory effect on immunoglobulin (Ig) production by B cells and tumor necrosis factor (TNF) production by monocytes. The activity of Hizikia fusiformis associated with polysaccharides which were extracted with ethanol and purified by ion-exchange and gel filtration chromatography, whose molecular weight was about 100 kDa. These results suggest that SWE has an immunomodulating activity on human lymphocytes and this ability might be useful for clinical application to treat several diseases such as tumors.

Stimulating activity of Chinese medicinal herbs on human lymphocytes in vitro.

The effects of eight kinds of Chinese medicinal herbs (CMH) on human lymphocytes was studied in vitro. The extract of Cinnamomum cassia presl markedly stimulated human lymphocytes to proliferate. Codonopsis pilosula, Oldenlandia diffusa and Rhizoma typhonii weakly stimulated. These extracts enhanced cytotoxic T-lymphocyte (CTL) activity, but failed to enhance natural killer (NK)-cell activity. The extracts of these CMHs have stimulatory effect on immunoglobulin (Ig) production by B-cells and interleukin(IL)-1 production by monocytes. These activities of Cinnamomun cassia presl extract are associated with glycoproteins, whose molecular weight was about 100 KDa. These results suggest that CMH extracts have a stimulating activity on human lymphocytes and these abilities could be used clinically for the treatment of diseases such as cancer.

Suppressive effect of Chinese medicinal herb, Acanthopanax gracilistylus, extract on human lymphocytes in vitro.

We studied the effect of a Chinese medicinal herb, Acanthopanax gracilistylus, extract (AGE), on human lymphocytes in vitro. AGE markedly suppressed the proliferative responses of human peripheral blood lymphocytes stimulated with mitogens concanavalin A (Con A) and Staphylococcus aureus Cowan I (SAC). Both T cell and B cell activities-production of interferon-gamma and immunoglobulin-were suppressed by AGE. The mechanism of AGE-induced suppression of lymphocytes is to arrest the cell cycle at the G0/G1 stage without a direct cytotoxic effect. AGE also suppressed the alloantigen-specific cytotoxic T lymphocyte response. However, natural killer cell activity was less sensitive to the suppressive activity of AGE. In contrast, AGE markedly enhanced monocyte function to produce cytokines. These activities of AGE were associated with a 60-kD protein which was sensitive to treatment with pronase E, but not with NaIO4. These results suggest that AGE has an immunomodulating activity on human lymphocytes and its properties could be clinically applied in the treatment of several diseases such as autoimmune and allergic diseases.

Chinese medicinal herb, Acanthopanax gracilistylus, extract induces cell cycle arrest of human tumor cells in vitro.

We investigated the effect of a Chinese medicinal herb, Acanthopanax gracilistylus (AG), extract (E) on the growth of human tumor cell lines in vitro. AGE markedly inhibited the proliferation of several tumor cell lines such as MT-2, Raji, HL-60, TMK-1 and HSC-2. The activity was associated with a protein of 60 kDa, which was purified by gel-filtration chromatography. Cell viability analyses indicated that the treatment with AGE inhibits cell proliferation, but does not induce cell death. The mechanism of AGE-induced inhibition of tumor cell growth involves arrest of the cell cycle at the G(0) / G(1) stage without a direct cytotoxic effect. The cell cycle arrest induced by AGE was accompanied by a decrease of phosphorylated retinoblastoma (Rb) protein. Furthermore, cyclin-dependent kinases 2 and 4 (Cdk2 and Cdk4), which are involved in the phosphorylation of Rb, were also decreased. These results suggest that AGE inhibits tumor cell growth by affecting phosphorylated Rb proteins and Cdks.

Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular.

The effect of eight different Chinese medicinal herbs (CMHs) on lymphocytes was studied in vitro using murine spleen cells. Among the studied eight CMHs, Astragalus membranaceus and Oldenlandia diffusa markedly stimulated murine spleen cells to proliferate. The responder cells for CMHs were B cells, because the response was depleted by the treatment of spleen cells with anti-immunoglobulin (i.g.) antibody and complement and after purification by nylon wool column. This response was not due to contamination by lipopolysaccharide (LPS), because CMHs could stimulate C3H/HeJ spleen cells which are low responders to LPS. CMHs enhanced the production of Ig. CMHs also enhanced the induction of allo-antigen specific cytotoxic T lymphocytes. However, CMHs had no effect on natural killer cells. Furthermore, CMHs stimulated macrophages to produce interleukin-6 and tumor necrosis factor. The electroelution of the proteins from SDS-PAGE gel showed that the active components of Oldenlandia diffusa had an apparent molecular weight of 90-200 kD and were sensitive to pronase E and NaIO4 treatment, suggesting glycoproteins in nature. These results suggest that CMHs have immunomodulating activity in vitro and this activity could be used clinically for the modulation of immune responses.