New Labdane-type diterpenoids and anti-inflammatory constituents from Hedychium coronarium.

Four new labdane-type diterpenoids: hedychicoronarin (1), peroxycoronarin D (2), 7ß-hydroxycalcaratarin A (3), and (E)-7ß-hydroxy-6-oxo-labda-8(17),12-diene-15,16-dial (4), have been isolated from the rhizomes of Hedychium coronarium, together with 13 known compounds (5-17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 3, 5, 6, and 10 exhibited inhibition (IC50 values ≤4.52 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3-6, 10, and 11 inhibited fMLP/CB-induced elastase release with IC50 values ≤6.17 µg/mL.

Overexpression of a secretory leukocyte protease inhibitor in human gastric cancer.

Complementary DNA microarrays have identified aberrantly expressed genes in patients with gastric cancer. One that encodes secretory leukocyte protease inhibitor (SLPI) is among the aberrantly expressed genes and is associated with metastasis in gastric cancers. We evaluated the potential of SLPI expression as a helpful biomarker for detection of gastric cancer. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. SLPI expression levels were determined by Northern and Western blot tests and quantitative-reverse transcriptase-polymerase chain reaction (Q-RT-PCR). Paraffin-fixed tumor tissues were used for immunohistochemistry study in 119 patients. A consistent result was obtained between all examinations except plasma SLPI. SLPI mRNA transcripts and protein were overexpressed in gastric cancer cells, and the depth of wall invasion was significantly greater in serosa-invading (T3 and T4) cancers compared to the serosa-free (T1 and T2) cancers. These enhanced expressions were significantly associated with lymph node metastasis, and were significantly higher in stages III and IV, and higher than those in stages I and II. Five-year survival of patients with lower expression of the SLPI gene was significantly better than among patients with a higher expression. To better understand the function of SLPI in human gastric cancer cells, isogenic SLPI overexpressing cell lines (AZ521) were prepared. The migratory and invasive abilities were increased 4.4-fold to 6.9-fold, or 3.0-fold to 4.1-fold, respectively, in SLPI-overexpressing cell lines. The results point to SLPI as a potential prognostic marker for gastric cancer and its function in cell invasion.

Adrenal cystic lesions: a clinicopathological analysis of 25 cases with proposed histogenesis and review of the literature.

Adrenal cystic lesions are uncommon and we analyzed clinical and pathologic features of 25 such cases from a single institute over 23 years. There were 16 pseudocysts, eight endothelial cysts, and one epithelial cyst. Seven of eight endothelial cysts were confirmed to be lymphangiomatous by D2-40 immunostaining. We suggest that pseudocysts and endothelial cysts may have different histogenesis. The proposed mesothelial origin of adrenal epithelial cyst cannot be confirmed in our example. Seven adrenal pseudocysts were associated with tumor, including two pheochromocytomas, one neuroblastoma, one adrenal cortical carcinoma, one adrenal cortical adenoma, one myelolipoma, and one schwannoma. The distinction of true cystic lesion from cystic neoplasm is important and requires thorough sampling of the specimens.

Acupuncture therapy results in immediate bronchodilating effect in asthma patients.

BACKGROUND: According to previous data on asthma in the English literature, there are some results that show encouraging effects of acupuncture improving pulmonary function in asthma patients. We designed a prospective randomized crossover controlled study to determine the efficacy of acupuncture in asthma patients. METHODS: Eighteen asthma patients with bronchodilator response >20% improvement of forced expiratory volume in 1 second (FEV1) were initially randomly assigned to receive 1 performance of real acupuncture (RA) or sham acupuncture (SA) in a blinded manner. After a washout period, the patients were crossed over. Spirometry was done and recorded before and after acupuncture. RESULTS: Sixteen of 18 patients completed the study. The mean (+/-SD) FEV1 values before and after RA were 1.52 +/- 0.45L and 1.67 +/- 0.40L, respectively (p < 0.001). The mean (+/-SD) FEV1 values before and after SA were 1.49 +/- 0.40L and 1.49 +/- 0.41L, respectively (p = 0.838, not significant). The percentage change in FEV1 values after RA was better than after SA (RA, 11.57 +/- 8.11%; SA, 0.32 +/- 7.76%; p = 0.003), while the bronchodilator response of FEV1 from simple inhalation bronchodilator was better than that for RA (p < 0.001). CONCLUSION: In asthma patients, acupuncture treatment may result in immediate improvement of FEV1, but the degree of improvement is less than that from inhalation bronchodilator.

Acupuncture resulting in immediate bronchodilating response in asthma patients.

There are some encouraging results in the English literature that show acupuncture resulting in an immediate improvement in pulmonary function, but there are also studies that have not demonstrated any benefit. We present 3 patients with persistent asthma who experienced immediate bronchodilatation after acupuncture without the use of any short-acting bronchodilator. After needle stimulation on selected acupoints, clinical symptoms such as dyspnea and wheezing improved. Pulmonary function test showed immediate improvement in forced expiratory volume in 1 second (FEV1), more than 20% as compared with baseline FEV1. Pulmonary function returned to baseline within 4 hours after acupuncture in 2 patients. From our observations of these 3 asthma patients, acupuncture may improve clinical dyspnea symptoms and performance on pulmonary function tests. Further large-scale controlled studies should be conducted to determine the effectiveness of acupuncture in the treatment of asthma.

Role of podoplanin expression in squamous cell carcinoma of upper aerodigestive tract.

Podoplanin, a type-1 transmembrane glycoprotein, was originally named due to its expression in renal podocytes of rats. It was subsequently detected in a variety of normal human tissues, including lymphatic endothelium. Although podoplanin has been identified as the endogenous ligand of C-type lectin-like receptor 2 (CLEC-2) on platelets, its physiological functions and pathways remain largely unknown. A role in lymphangiogenesis has been suggested, since podoplanin-deficient mice were found to die at birth with a phenotype of dilated, malfunctioning lymphatic vessels and lymphedema. Podoplanin is invariably expressed in some tumors, such as lymphangioma, seminoma and follicular dendritic cell tumor, but tumor cell expression of podoplanin is highly variable in squamous cell carcinoma (SCC). It has been found that high podoplanin expression is associated with lymph node metastasis and poor prognosis in SCC of the upper aerodigestive tract. Now there is growing evidence that podoplanin is also involved in carcinogenesis, cell motility, tumor invasiveness, platelet aggregation and hematogenous metastasis. Additionally, animal studies confirmed some in vivo effects of podoplanin-overexpressing tumors, including formation of more tumor lymphatic vessels, larger lymph node metastases, more platelet aggregation, and more pulmonary metastases. Several recently developed anti-podoplanin antibodies, such as NZ-1, P2-0 and hP2-0, have been shown to attenuate podoplanin-induced platelet aggregation and prevent experimental hematogenous metastasis in nude mice. These antibodies may be applied in preclinical and clinical studies to evaluate the possibility of podoplanin-targeted therapy.

Graptopetalum paraguayense ameliorates chemical-induced rat hepatic fibrosis in vivo and inactivates stellate cells and Kupffer cells in vitro.

BACKGROUND: Graptopetalum paraguayense (GP) is a folk herbal medicine with hepatoprotective effects that is used in Taiwan. The aim of this study was to evaluate the hepatoprotective and antifibrotic effects of GP on experimental hepatic fibrosis in both dimethylnitrosamine (DMN)- and carbon tetrachloride (CCl(4))-induced liver injury rats. METHODS: Hepatic fibrosis-induced rats were fed with the methanolic extract of GP (MGP) by oral administration every day. Immunohistochemistry, biochemical assays, and Western blot analysis were performed. The effects of MGP on the expression of fibrotic markers and cytokines in the primary cultured hepatic stellate cells (HSCs) and Kupffer cells, respectively, were evaluated. RESULTS: Oral administration of MGP significantly alleviated DMN- or CCl(4)-induced liver inflammation and fibrosis. High levels of alanine transaminase, aspartate transaminase, bilirubin, prothrombin activity and mortality rates also decreased in rats treated with MGP. There were significantly decreased hydroxyproline levels in therapeutic rats compared with those of the liver-damaged rats. Collagen I and alpha smooth muscle actin (α-SMA) expression were all reduced by incubation with MGP in primary cultured rat HSCs. Furthermore, MGP induced apoptotic cell death in activated HSCs. MGP also suppressed lipopolysaccharide-stimulated rat Kupffer cell activation by decreasing nitric oxide, tumor necrosis factor-α and interleukin-6 production, and increasing interleukin-10 expression. CONCLUSIONS: The results show that the administration of MGP attenuated toxin-induced hepatic damage and fibrosis in vivo and inhibited HSC and Kupffer cell activation in vitro, suggesting that MGP might be a promising complementary or alternative therapeutic agent for liver inflammation and fibrosis.

Effects of glutamine administration on inflammatory responses in chronic ethanol-fed rats.

The purpose of this study was to investigate the effects of glutamine supplementation on inflammatory responses in chronic ethanol-fed rats. Male Wistar rats weighing about 160 g were divided into five groups. Two groups were fed a normal liquid diet and three groups were fed a glutamine-containing liquid diet. After 1 week, one of the normal liquid diet groups was fed an ethanol-containing liquid diet (CE), and the other group served as the control (CC) group. At the same time, one of the glutamine-containing liquid diet groups was continually fed the same diet (GCG), but the other two groups were fed ethanol-containing diet supplemented with glutamine (GEG) or without glutamine (GE). The following items were analyzed: (1) liver function, (2) cytokine contents, and (3) hepatic oxidative stress. The activities of aspartate transaminase (AST) and alanine transaminase (ALT) and levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the CE group had significantly increased. In addition, hepatic cytochrome P450 2E1 (CYP2E1) expression had significantly increased in the CE, GE and GEG groups. However, the activities of AST and ALT and levels of TNF-α and IL-1ß in the GE group were significantly lower than those of the CE group. The results suggest that the plasma inflammatory responses of rats fed an ethanol-containing liquid diet for 7 weeks significantly increased. However, pretreatment with glutamine improved the plasma inflammatory responses induced by ethanol.

Tumor cell expression of podoplanin correlates with nodal metastasis in esophageal squamous cell carcinoma.

Podoplanin is a mucin-like glycoprotein expressed in the lymphatic endothelium. It has been suggested to play a role in lymphangiogenesis, since podoplanin deficient mice were found to have dilated malfunctioning lymphatic vessels and lymphedema. High podoplanin expression in tumor cells was found to correlate with lymph node metastasis and poor clinical outcome in patients with oral squamous cell carcinoma (SCC). However, the prognostic significance of podoplanin expression in esophageal SCC remains unexplored. Herein, we studied podoplanin expression in 59 patients who underwent surgical resection of esophageal SCC, with 43 of them preceded by preoperative concurrent chemoradiotherapy (CCRT). We found that high podoplanin expression strongly correlated with clinical nodal metastasis (cN1; p=0.0063), which was associated with short survival (p=0.012). However, there was no direct association between high podoplanin expression and short survival. We also found that lymphatic vessel invasion in the resected esophagus was strongly associated with pathological nodal metastasis (pN1; p=0.00092). Our results suggest that podoplanin could also play a role in tumor aggressiveness in esophageal SCC, as well as in oral SCC.

Thymic lymphoepitheliomalike carcinoma in children: clinicopathologic features and molecular analysis.

Thymic lymphoepitheliomalike carcinoma (LELC) in children is extremely rare and we report 2 such cases with molecular analysis of Epstein-Barr virus (EBV) and its encoded latent membrane protein-1 as well as a literature review. Both of our patients were male, presented with a huge anterior mediastinal mass, expired within a year after diagnosis despite treatment. There were altogether 9 cases of thymic LELC in children. Their common clinical features include a male predominance, large tumor size, advanced clinical stage, and poor clinical outcome. All cases were associated with EBV and nearly half developed concurrent hypertrophic osteoarthropathy (HOA). Thymic LELC in children is an aggressive EBV-associated malignant tumor frequently accompanied by HOA. We proposed that EBV might play a role in the development of HOA through the interactions of latent membrane protein-1, vascular endothelial growth factor, and cyclooxygenases-2.