The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer

CD44 is a transmembrane glycoprotein and surface receptor for hyaluronan that is involved in the response of cells to their microenvironment. CD44 splice variants play roles in carcinogenesis, differentiation, and lymph node metastasis and are predictive of the prognosis for various carcinomas, including gastric cancer. Current data suggest that gastric tissue stem cells and gastric cancer stem cells both express the splice variant, CD44v9. Overall, the data regarding the alterations that occur in CD44 and its splice variants in response to acute and chronic infection with Helicobacter pylori are scant and poorly elucidated in terms of possible changes in expression that occur in gastric cancer precursor lesions, such as chronic atrophic gastritis, pyloric metaplasia and intestinal metaplasia. In this study, we discuss the available data and suggest which new data would likely be useful in clinical practice. We also discuss the potential for CD44-targeted therapeutic strategies in gastric cancer. CD44 and its splice variants are positively associated with the initiation and progression of gastric cancer and may also play important roles in diagnosis, therapy and prognosis. CD44 research has been active but fragmented, and it may offer new therapeutic approaches to gastric cancer.     

PI3K/AKT pathway alterations are associated with clinically aggressive and histologically anaplastic subsets of pilocytic astrocytoma

Pilocytic astrocytomas (PA) are well-differentiated gliomas having a favorable prognosis when compared with other diffuse or infiltrative astrocytomas. Molecular genetic abnormalities and activation of signaling pathways associated with clinically aggressive PA and histologically anaplastic PA have not been adequately studied. We performed molecular genetic, gene expression, and immunohistochemical studies using three PA subsets, including conventional PA (n?=?43), clinically aggressive/recurrent PA (n?=?24), and histologically anaplastic PA (n?=?25). A clinical diagnosis of NF1 was present in 28% of anaplastic PA. Molecular cytogenetic studies demonstrated heterozygous PTEN/10q and homozygous p16 deletions in 6/19 (32%) and 3/15 (20%) cases of anaplastic PA, respectively, but in neither of the two other groups. BRAF duplication was identified in 33% of sporadic anaplastic PA and 63% of cerebellar examples. BRAF (V600E) mutation was absent in four (of 4) sporadic cases lacking duplication. IDH1(R132H) immunohistochemistry was negative in 16 (of 16) cases. Neither PDGFRA nor EGFR amplifications were present. pERK staining levels were similar among the three PA subsets, but a stepwise increase in cytoplasmic pAKT and to a lesser extent pS6 immunoreactivity was noted by immunohistochemistry in aggressive PA groups. This was particularly true in histologically anaplastic PA when compared with conventional PA (p?相似文献   

蜕皮甾酮对高糖培养大鼠肾小球系膜细胞影响机制的研究

观察蜕皮甾酮对高糖环境下大鼠肾小球系膜细胞（MCs）细胞外基质的影响并初步探讨其可能的作用机制。方法：体外培养大鼠Mes细胞株,分低糖组、高糖组、甘露醇组、乙醇对照组、高糖＋蜕皮甾酮组（EDS组）、高糖＋苯那普利组,分别作用12h、24h、48h,免疫细胞化学法检测细胞Col1V蛋白的表达,RT—PCR检测TGF—β1及Smad7mRNA的表达。结果：（1）c01Ⅳ表达的变化：与低糖组比较,高糖组colⅣ表达显著增加（P〈0．01）;与高糖组比较,EDS组及苯那普利组Col1V表达显著减少（P〈0．01）,EDS组与苯那普利组无显著差异（P〉0．05）;（2）TGF—p1及Smad7mRNA的表达：与低糖组比较,高糖组24hSmad7基因表达明显增加（P〈0.01）,24h、48hTGF—B1基因表达均显著增加（P〈0．01）;与高糖组比较,24h、48hEDS组及苯那普利组Smad7基因表达均明显增加（P〈0．01）,TGF—B1基因表达均显著减少（P〈0．01）,EDS组与苯那普利组之间Smad7、TGF—B1基因表达无显著差异（P〉0．05）。结论：（1）蜕皮甾酮能减少高糖培养大鼠MCs细胞外基质的增加。（2）蜕皮甾酮能下调TGF—β1 mRNA的表达、上调Smad7 mRNA的表达,从而发挥对肾脏的保护作用。     

去磷酸化NFATc蛋白的相对表达与四逆汤治疗心力衰竭的机制分析

目的:分析Ca2+-钙调神经磷酸酶-活化T细胞核因子(Ca2+/CaN-NFATc)信号转导通路在四逆汤治疗心衰过程中的机制。方法:采用SPF级SD大鼠50只用连续腹腔注射盐酸阿霉素的方法复制大鼠心力衰竭模型,待造模成功后将动物分为空白对照组、模型对照组与四逆汤治疗组(高、中、低剂量组),用四逆汤水煎液治疗8天后,分别检测心肌组织CaN活性、去磷酸化NFATc蛋白的相对表达、钙含量、及IL-2和IL-4的含量。结果:治疗组2.8g/kg组血清CaN活性、去磷酸化NFATc蛋白的相对表达、IL-2、IL-4含量均显著降低,Ca2+含量显著升高(P(0.05)。结论:Ca2+/CaN-NFATc信号转导通路在四逆汤治疗心衰过程中发挥重要的调控作用。     

钙调磷酸酶在附子苷对心衰调控过程中的靶向研究

目的:分析CaN信号分子在附子苷治疗心衰过程中的靶向作用。方法:采用SPF级SD大鼠50只用连续腹腔注射盐酸阿霉素的方法复制大鼠心力衰竭模型,待造模成功后将动物分为空白对照组、模型对照组与附子苷治疗组(高、中、低剂量组),用附子苷配制液治疗8天后,用CaN试剂盒检测大鼠血清的CaN的含量。结果:治疗组0.7mg/kg、0.35mg/kg剂量组血清CaN含量均明显高于模型组(P(0.05)。结论:在用附子有效成分—附子苷对心衰进行治疗过程中,CaN信号分子起重要的靶向作用。     

Anti-fatigue activity of polysaccharides from the fruits of four Tibetan plateau indigenous medicinal plants

Ethnopharmacological relevance

The fruits of Hippophae rhamnoides L., Lycium barbarum L., Lycium ruthenicum Murr. and Nitraria tangutorum Bobr. are traditional medicinal food of Tibetans and used to alleviate fatigue caused by oxygen deficiency for thousands of years. The present study focused on exploiting natural polysaccharides with remarkable anti-fatigue activity from the four Qinghai-Tibet plateau characteristic berries.

Materials and methods

The fruits of Hippophae rhamnoides, Lycium barbarum, Lycium ruthenicum and Nitraria tangutorum were collected from Haixi national municipality of Mongol and Tibetan (N 36.32°, E98.11°; altitude: 3100 m), Qinghai, China. Their polysaccharides (HRWP, LBWP, LRWP and NTWP) were isolated by hot-water extraction, and purified by DEAE-Cellulose ion-exchange chromatography. The total carbohydrate, uronic acid, protein and starch contents of polysaccharides were determined by a spectrophotometric method. The molecular weight distributions of polysaccharides were determined by gel filtration chromatography. Their monosaccharide composition analysis was performed by the method of 1-phenyl-3-methyl-5-pyrazolone (PMP) pre-column derivatization and RP-HPLC analysis. HRWP, LBWP, LRWP and NTWP (50, 100 and 200 mg/kg) were orally administrated to mice once daily for 15 days, respectively. Anti-fatigue activity was assessed using the forced swim test (FST), and serum biochemical parameters were determined by an autoanalyzer and commercially available kits; the body and organs were also weighted.

Result

LBWP, LRWP and NTWP were mainly composed of glucans and some RG-I pectins, and HRWP was mainly composed of HG-type pectin and some glucans. All the four polysaccharides decreased immobility in the FST, and the effects of LBWP and NTWP were demonstrated in lower doses compared with HRWP and LRWP. There was no significant difference in liver and heart indices between non-treated and polysaccharide-treated mice, but the spleen indices were increased in LBWP and NTWP (200 mg/kg) group. Moreover, the FST-induced reduction in glucose (Glc), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increase in creatine phosphokinase (CK), lactic dehydrogenase (LDH), blood urea nitrogen (BUN), triglyceride (TG) and malondialdehyde (MDA) levels, all indicators of fatigue, were inhibited by HRWP, LBWP, LRWP and NTWP to a certain extent while the effects of LBWP and NTWP were much better than that of HRWP and LRWP at the same dosage.

Conclusion

Water-soluble polysaccharides HRWP, LBWP, LRWP and NTWP, from the fruits of four Tibetan plateau indigenous berry plants, significantly exhibited anti-fatigue activities for the first time, through triglyceride (TG) (or fat) mobilization during exercise and protecting corpuscular membrane by prevention of lipid oxidation via modifying several enzyme activities. Moreover, it is demonstrated that LBWP and NTWP are more potent than HRWP and LRWP, which were proposed to be applied in functional foods for anti-fatigue and antioxidant potential.