Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas.METHODS The immunohistochemical SP method was used to detect the expression of Coxsaekie and Adenovirus receptor in 48 cases of renalcell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue.RESULTS The positive rates of CAR were 100% in 12 cases of para-tumcr normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P＜0.05). The grades of the tumor were as follows: 22 in Grade Ⅰ, 17in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%,23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P＜0.05). In addition, the number of the cases in stages Ⅰ to ⅣV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P＜0.05).CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.     

从基础研究中探寻前列腺癌新的治疗靶向

Since 1990, prostate cancer （PCa） has been the most common non-skin cancer in American men, even snrpassing lung cancer. Because the mean age of the American population continues to increase while mortality from other causes continues to decrease, the incidence and mortality of PCa are likely to slay relative high level because the incidence of PCa rises significantly in men over 50-55 years old.[第一段]     

Carthamus tinctorius L. extract activates insulin‐like growth factor‐I receptor signaling to inhibit FAS‐death receptor pathway and suppress lipopolysaccharides‐induced H9c2 cardiomyoblast cell apoptosis

Carthamus tinctorius L. (Compositae) is used in Chinese medicine to treat heart disease and inflammation. In our previous study, we found that C. tinctorius L. inhibited lipopolysaccharides (LPS)‐induced tumor necrosis factor‐alpha (TNF‐α) activation, JNK expression, and apoptosis in H9c2 cardiomyoblast cells. The present study was performed to investigate the protective effect of C. tinctorius extract (CTF) on LPS‐challenged H9c2 myocardioblast cell and to explore the possible underlying mechanism. Cell viability assay showed that LPS treatment decreased the cell viability of H9c2 cell, whereas CTF treatment reversed LPS cytotoxicity in a dose‐dependent manner, especially in the LPS + CTF 25 (μg/mL) group. LPS treatment‐induced apoptosis was determined by transferase‐mediated dUTP nick end labeling assay, and by Western blot. LPS‐induced apoptotic bodies were decreased following CTF treatment. Expression of TNF‐α, FAS‐L, FAS, FADD, caspase‐8, BID, and t‐BID was significantly increased in LPS‐treated H9c2 cells. In contrast, it was significantly suppressed by the administration of CTF extract. In addition, CTF treatment activates antiapoptotic proteins, Bcl‐2 and p‐Bad, and downregulates Bax, cytochrome‐c, caspase‐9, caspase‐3, and apoptosis‐inducing factor expression. Furthermore, CTF exerted cytoprotective effects by activating insulin‐like growth factor‐I (IGF‐I) signaling pathway leading to downregulation of the apoptotic proteins involved in FAS death receptor pathway. In addition, AG1024 and IGF‐I receptor (IGF‐IR) inhibitor and siRNA silencing reverses the effect of CTF implying that CTF functions through the IGF‐IR pathway to inhibit LPS‐induced H9c2 apoptosis. These results suggest that treatment with CTF extract prevented the LPS‐induced apoptotic response through IGF‐I pathway.     

Molecular targeting of liposomal nano-particles to lymphatic system

Conventional liposomal drug delivery has been associated with obvious limitations, such as a rapid absorption by the recticulo-endothelial system in the liver and spleen, a short circulation time and a low therapeutic efficacy. Various modifications of liposomal drugs have been developed to prolong the duration of actions of the drugs at target sites, reduce its adverse effects and increase therapeutic index of drugs such as polymeric conjugation and polymeric fixation on the surface of a liposome. The lymphatic system is an important highway to spread the metastasis of most human cancers including breast, colon, and lung, ovarian and prostate. To eradicate those metastatic cancer cells from the lymphatic system, several efforts have been made to develop new and efficient lymphatic targeting drug delivery systems in order to achieve a high initial lymphatic uptake and lymph node localization. Recently, molecule targeting of liposome to lymphatic system may enhance therapeutic efficacy by improving the initial lymphatic uptake and the lymph nodal retention of liposomes such as the ligand-receptor and antibodies binding on the surface of liposome. This article aims to review the emerging liposomal drug, which is targeting the lymphatic system. The significant factors associated with targeting liposomal drugs will also be discussed in more detail in this review.     

Risk factors for recurrence of group B streptococcus colonization in a subsequent pregnancy

OBJECTIVE: To document rates of recurrent group B streptococci (GBS) colonization in women with previous GBS colonization in an initial pregnancy and to assess maternal risk factors associated with recurrence. METHODS: A retrospective, longitudinal study was performed in a teaching hospital on women with GBS colonization who were pregnant between 2002 and 2006 and had at least one subsequent pregnancy during the same time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 251 women. The rate of recurrence was estimated for GBS colonization in the pregnancy after the index pregnancy for GBS colonization. Multivariable regression models were constructed to model recurrence of GBS colonization in a subsequent pregnancy as functions of potential predictors to estimate relative risks and confidence intervals. RESULTS: The rate of recurrence of GBS colonization in the pregnancy subsequent to the index pregnancy was 38.2% (95% confidence interval 33.5-42.9%). Multivariable regression models showed that the time interval between the two pregnancies and the intensity of GBS colonization from the index pregnancy were predictive of recurrent GBS colonization. CONCLUSION: More than one third of women had recurrent GBS colonization in a subsequent pregnancy. These findings should assist clinicians in counseling women with GBS colonization about their risk for recurrence, the importance of appropriate prenatal GBS screening in a subsequent pregnancy, and intrapartum antibiotic prophylaxis for unknown GBS status.     

Tumor necrosis factor-alpha converting enzyme in the human placenta throughout gestation

Ectodomain shedding of epidermal growth factor receptor ligands such as transforming growth factor- alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HBEGF), and amphiregulin (AREG) is considered to be important during implantation. Tumor necrosis factor-alpha converting enzyme (TACE) has been suggested as the major sheddase for these molecules. The objectives of this study are (1) to characterize the expression of TACE in the human placenta throughout gestation; (2) to determine the association between the expression of TACE with TGF-alpha, HBEGF, and AREG; (3) to ascertain whether TACE mediates TGF-alpha, HBEGF, and AREG shedding; and (4) to examine the effect of hypoxia on the expression of TACE. By analyzing a total of 55 villous samples representing different gestational ages, the authors found that TACE was continuously expressed in the placentas throughout gestation and that the levels of TACE were positively correlated with the levels of TGF-alpha, HBEGF, and AREG. Preadministration of a TACE inhibitor in villous explant cultures or transfection of cytotrophoblastic cells with TACE-specific small interference RNA decreased the shedding of HBEGF and AREG. Moreover, hypoxia (2% O(2)) caused an increase in the levels of TACE mRNA and protein in villous explants and primary cytotrophoblastic cells in vitro. These results indicate that oxygen regulates the expression of TACE and that TACE may be important for placental development during human pregnancy.     

Oxygenated cembranoids from a Formosan soft coral Sinularia gibberosa

Chemical investigation of a Formosan soft coral, Sinularia gibberosa, has led to the isolation of eight oxygenated cembranoids, 1- 8, including seven new compounds, gibberosenes A-G ( 2- 8). None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 1 significantly inhibited the accumulation of the pro-inflammatory COX-2 protein of the LPS-stimulated RAW264.7 macrophage cells.     

Cyclopeptides with anti-inflammatory activity from seeds of Annona montana

Four new cyclopeptides, cyclomontanins A-D (1- 4), annomuricatin C (5), and (+)-corytuberine were isolated from a methanol extract of Annona montana seeds. Their structures were elucidated by 2D NMR analysis, ESIMS/MS fragment evidence, and chemical means. The structure of 1 was confirmed by synthesis. Compounds 1, 3, and 4 exhibited anti-inflammatory activity in vitro using the J774.1 macrophage model.     

Petroleum ether extract of Cnidium monnieri ameliorated scopolamine-induced amnesia through adrenal gland-mediated mechanism in male rats

AIM: Our previous study indicated petroleum ether layer of Cnidium monnieri L. Cuss. (CM) and its ingredient osthole could alleviate scopolamine-induced amnesia in female rats. MATERIALS AND METHODS: Hence, this study was desired to investigate the mechanism of the ameliorating effects of petroleum ether layer of CM on the performance impairment of inhibitory avoidance task and Morris water maze induced by scopolamine in male rats. RESULTS: CM at 0.1-0.6g/kg orally administered 60 min before the training trial ameliorated the scopolamine-induced performance impairment on inhibitory avoidance learning and water maze in male rats. Only adrenalectomy but not peripheral cholinergic antagonist scopolamine methylbromide and catecholaminergic neurotoxin 6-hydroxydopamine blocked the ameliorating effects of CM on scopolamine-induced performance impairment in rats. CONCLUSION: Therefore, we demonstrated that the ameliorating effects of CM on scopolamine-induced performance impairment may be related to activating the adrenal gland and central acetylcholingeric neuron, instead of peripheral nervous system.     

Inhibition of pro-inflammatory mediators and tumor cell proliferation by Anisomeles indica extracts

Anisomeles indica (L.) Kuntze (Labiatae), is a traditional anti-inflammatory herb used in Taiwan. The aqueous and methanolic extracts of whole plants, leaves, flowers and stems; and chloroform and n-butanol fractions of methanol extract, from A. indica were investigated for their anti-inflammatory activity on murine peritoneal macrophages. In addition, the tumor cells proliferation inhibition activities of these extracts were also evaluated against a panel of tumor cell lines such as Colon 205, PC 3, HepG2 and MCF 7. Treatment with A. indica extracts did not reduce cell viability at any dose used. However, all the extracts significantly inhibited the enhanced production of NO radicals, and pro-inflammatory cytokines (TNF-alpha, and IL-12) induced by LPS/IFN-gamma in a dose-dependent manner. Furthermore, methanolic extracts of leaves and flowers significantly and dose-dependently arrest mitogen-stimulated spleen cells in G0/G1 stage, in addition to their cell proliferation inhibition against Colon 205, MCF 7 and PC 3 by 94, 82; 98, 71; 82, 98%, respectively, at 200 microg/mL concentration. This is the first report on A. indica extracts for their growth inhibitory activities, against inflammatory mediator production, and human tumor cell lines, colon, prostate, hepatoma and breast cells proliferation.