Serum müllerian-inhibiting substance in Down's syndrome pregnancies

BACKGROUND: To examine whether maternal serum levels of müllerian-inhibiting substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS: Case-control study was conducted using stored serum from an antenatal screening programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20 degrees C storage together with 125 unaffected controls individually matched for maternal age, weeks of gestation and duration of storage. Results were expressed in multiples of the gestation-specific median value (MoM) in controls. RESULTS: The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically significant correlation between MIS and pregnancy-associated plasma protein-A (P < 0.05). MIS levels were elevated in pregnancies where assisted reproduction techniques had been used. CONCLUSION: There is no evidence for a substantial reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study provides useful information regarding serum MIS levels in pregnancy.     

Predicting Failure Load of the Femur with Simulated Osteolytic Defects using Noninvasive Imaging Technique in a Simplified Load Case

Currently, there is no proven sensitive or specific method for predicting pathological fracture of the femur. The clinical management of lytic femoral metastases is based on geometric measurement of the bone, of the defect, or both. However, the mechanical behavior of a structure depends on both its material and geometric properties. Our hypothesis is that a change in bone structural properties as the result of tumor induced osteolysis determines the fracture risk in bones with skeletal metastases. We developed a method of QCT (Quantitative Computed Tomography) combined with engineering beam analysis as a noninvasive tool for measuring the material and geometric properties of the femur with simulated lytic defects in the intertrochanteric region. In this ex-vivo study we prove that engineering beam structural analysis applied to serial transaxial QCT scans through human femora with simulated lytic defects at the proximal femur predicts the load at failure and location of fracture better than current clinical guidelines. Structural rigidity measured by QCT in this study may be used to predict the load carrying capacity of femurs with metastatic defects and, furthermore, may be used when the tumor has weakened the bone sufficiently such that pathological fracture is imminent and prophylactic stabilization is necessary.

High-degree tumor budding and podia-formation in sporadic colorectal carcinomas with K-ras gene mutations

In vitro ras activation enhances the epithelial-mesenchymal transition of colorectal carcinoma cells. But ras effects are known to be highly dependent on cell types and the tissue context. Therefore, this study was made to test the hypothesis that in clinical colorectal carcinoma specimens, aggressive invasion phenotypes, specifically tumor budding and podia formation, would correlate with K-ras gene mutations. In a series of 95 clinically sporadic primary colorectal carcinomas collected ad hoc, tumor budding and podia formation were counted using pan-cytokeratin immunohistochemistry, and K-ras gene mutations in codons 12 and 13 were determined. Consistent with the hypothesis, tumor budding and podia formation were observed to be significantly higher in the 32 (34.7%) of the tumors with K-ras gene mutations (29 mutations in codon 12, 3 in codon 13), and this correlation was observed independent of the patterns of invasion (expansive versus infiltrative). Microsatellite status, numbers of losses of heterozygosity, adenomatous polyposis coli and p53 gene mutations, and degree of promoter methylations (CIMP status) were not associated with K-ras gene mutations. Besides their effects on the tumor cell cycles, oncogenic K-ras gene mutations in colorectal carcinomas could be important for aggressive tumor invasion. This may be important in metastasizing disease and could provide a rationale for developing drugs that interrupt ras-signaling cascades.     

Abnormal fragile histidine triad (Fhit) expression in invasive cervical adenocarcinoma: association with tumor aggressiveness

The fragile histidine triad (FHIT) gene is a candidate tumor suppressor gene. Aberrant expression of the encoded protein and inactivation of FHIT correlate with several clinicopathological parameters in various tumor types, including cervical cancer, but Fhit expression has rarely been studied in cervical adenocarcinoma. We assessed Fhit protein expression in 35 surgical specimens of invasive adenocarcinomas of the uterine cervix and investigated whether expression alteration on immunohistochemistry staining is associated with important clinicopathological features. Considerably reduced or absent Fhit staining was observed in 11 cancers (31.4%). By univariate analysis, Fhit protein expression was significantly associated with nodal status (P = .002), histologic grade (P = .000), and International Federation of Gynecology and Obstetrics stage (P = .032). Depth of invasion, tumor size, or parametrial invasion did not show important association with Fhit. Lymph node status, International Federation of Gynecology and Obstetrics stage, and histologic grade are known prognostic factors of cervical adenocarcinoma, and Fhit status on immunohistochemistry staining demonstrated significant association with tumor aggressiveness. Staining of biopsy specimens for Fhit is worthy of study as a prognostic tool.     

Cooperation between CD4 and CD8 T cells for anti-tumor activity is enhanced by OX40 signals

The relative contribution of OX40 (CD134) to priming of CD8 T cells in complex systems where CD4 and CD8 cells respond and cooperate together is not clear. We previously found that OX40 expressed on tumor-reactive CD8 T cells controls their initial persistence when adoptively transferred in vivo and is required for delayed tumor growth. We now show that exogenous stimulation of OX40 with agonist antibody augments its ability to suppress the growth of new as well as established tumors, correlating with marked expansion of adoptively transferred CD8 T cells. Concomitantly, anti-OX40 strongly enhanced the number of tumor antigen-reactive CD4 T cells. Moreover, the augmented accumulation of CD8 T cells was prevented in animals lacking MHC class II or depleted of CD4 cells and did not occur in OX40-deficient animals receiving wild-type CD8 cells, demonstrating that non-CD8 cells are the major target of OX40 signals. These results suggest that while OX40 signaling to a CD8 T cell can control its expansion, OX40 expressed on non-CD8 cells strongly influences CD8 priming and in vivo activity. OX40 therefore represents an important signal for allowing effective cooperation between CD4 and CD8 cells and for promoting cell interplay and tumor rejection where CD8 activity is limiting.     

Activities of erythropoietin on tumors: an immunological perspective

There is a growing interest in the non-erythropoietic, tissue-protective and restorative actions of erythropoietin (EPO). While studies in this field have indicated that EPO can ameliorate chemotherapy-induced peripheral neuropathy and cardiotoxicity, the issue whether EPO can positively or negatively affect cancer patients is a hot one. In this debate, many activities of EPO are being considered, including tissue/neuroprotection, angiogenesis, anti-inflammatory activity, growth promotion, and inhibition of apoptosis. However, few studies have explored the interactions of EPO with the immune system. A study in this issue of the European Journal of Immunology by Katz et al. adds one new piece to the puzzle by showing that EPO can stimulate B cell-mediated immunity.     

CD4+ CD25high regulatory T cells reduce T cell transendothelial migration in cancer patients

Cell-mediated immunity is thought to be the main mechanism of anti-tumour responses of the host, but it is not known if cancer disease affects T cell recruitment from blood to tissues. Therefore, we compared Heliobacter pylori-induced T cell transendothelial migration (TEM) in H. pylori-infected gastric carcinoma patients, colon and lung carcinoma patients and healthy volunteers. H. pylori induced significant T cell migration from all groups. However, there was a dramatic reduction of T cell TEM in gastric carcinoma patients (80%) compared to healthy individuals. A similarly reduced transmigration was also seen in colon and lung carcinoma patients. We found significantly increased frequencies of T(reg) cells in the blood of gastric carcinoma patients compared to healthy individuals, and depletion of T(reg) cells from the blood of these patients prior to TEM restored T cell migration. The effect of T(reg) cells was largely dependent on cell-cell contact, but not on IL-10 or TGF-beta. In addition, the presence of T(reg) cells led to reduced T cell attachment to endothelium and decreased production of T cell-recruiting chemokines during TEM. In conclusion, T(reg) cell-mediated reduction of T cell TEM may reduce T cell recruitment in patients with epithelial malignancies, thereby hampering anti-tumour responses.     

神经节苷脂联合鼠神经生长因子对早产儿脑损伤后血清神经损伤标志物的影响

目的观察神经节苷脂联合鼠神经生长因子对早产儿脑损伤后血清神经损伤标志物的影响。方法选取我院胎龄均<37周的脑损伤患儿78例,随机分为对照组和试验组,每组39例。对照组给予胞二磷胆碱注射液0.125 g,每天1次,静脉滴注;试验组在对照组的基础上给予单唾液酸四己糖神经节苷脂钠注射液20 mg+注射用鼠神经生长因子18μg,每天1次,静脉滴注。2组患儿均治疗14 d。出生24 h内和出生14 d内收集血液标本,测定血清髓鞘碱性蛋白(MBP)、S^-100β蛋白、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和Toll样受体-4(TLR-4)水平,同时比较2组患者的临床疗效和药物不良反应发生情况。结果治疗后,试验组和对照组的总改善率分别为94.87%(37例/39例)和76.92%(30例/39例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的血清MBP分别为(2.01±0.58)和(2.46±0.67)μg·L^-1,S^-100β分别为(0.69±0.28)和(0.91±0.35)μg·L^-1,血清TNF-α分别为(2.04±1.03)和(3.15±1.26)μg·L^-1,IL-6分别为(161.78±44.18)和(257.63±51.36)ng·L^-1,TLR-4分别为(8.45±4.37)和(11.68±4.94)pg·m L^-1,意识恢复时间分别为(2.30±0.57)和(3.21±0.64)d,吸吮能力恢复时间分别为(4.17±0.42)和(5.01±0.45)d,原始反射恢复时间分别为(4.23±0.48)和(6.85±0.59)d,肌张力恢复时间分别为(4.68±0.49)和(7.04±0.53)d,差异均有统计学意义(均P<0.05)。试验组的药物不良反应主要有胃肠道反应及发热,药物不良反应发生率为10.26%(4例/39例);对照组的药物不良反应主要有胃肠道反应、躁动及发热,药物不良反应发生率为12.82%(5例/39例),差异无统计学意义(P>0.05)。结论神经节苷脂联合鼠神经生长因子对脑损伤早产儿的临床疗效确切,有利于缩短恢复时间,改善神经功能,且药物安全性高。     

p53介导蜕膜化受损致复发性流产的研究进展

复发性流产（RSA）病因复杂,约50%的RSA患者病因不明,其中由于蜕膜化受损所致的胚胎反复丢失成为学者关注的焦点。p53通过参与多种信号通路介导蜕膜化受损从而引发RSA。其中p53/p21信号通路过度激活可干扰细胞周期调控因子的表达,使细胞周期进入停滞状态,蜕膜多倍体化障碍,转而促进细胞凋亡,影响胚胎着床。而在雌二醇（E2）/p53-白血病抑制因子（LIF）-信号转导和转录激活因子3（STAT3）信号通路中,p53在雌激素的协同作用下促进植入期子宫内膜腺体分泌LIF,并激活JAK/STAT信号通路,为胚胎着床创造有利条件。研究表明,参与调控p53信号通路的长链非编码RNA（lncRNA）功能异常及p53通路基因多态性均可影响p53的活性,从而影响蜕膜化及妊娠结局。现就近年来国内外p53蛋白家族及其通路参与蜕膜化的相关研究进行综述。