Development and evaluation of the essential oil from Magnolia fargesii for enhancing the transdermal absorption of theophylline and cianidanol

To improve the skin permeation of theophylline and cianidanol ((+)-catechin), the essential oil of Magnolia fargesii was evaluated using in-vitro and in-vivo permeation techniques. Oxygenated monoterpenes and sesquiterpenes are the major components of M. fargesii essential oil. The in-vitro permeation of theophylline and cianidanol was significantly enhanced after treatment with M. fargesii essential oil. The essential oil increased the in-vivo skin deposition of cianidanol but not theophylline. On the other hand, in-vivo microdialysis showed a higher subcutaneous theophylline amount after essential oil treatment. In-vitro cell viability and prostaglandin E(2) release by skin keratinocytes indicated that there was low or negligible cytotoxicity by M. fargesii essential oil. The in-vivo skin tolerance study determined by transepidermal water loss and colorimetry confirmed that no irritation of the skin was detected when using M. fargesii essential oil.     

C5a differentially stimulates the ERK1/2 and p38 MAPK phosphorylation through independent signaling pathways to induced chemotactic migration in RAW264.7 macrophages

We elucidate the roles of various protein kinases involved in complement 5a (C5a)-induced cell migration. Results showed that extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (P13K) were necessary for C5a-induced migration, whereas protein kinase C and c-Jun N-terminal kinase (JNK) were nonessential. C5a-induced migration was also suppresses by phospholipase C (PLC) inhibitor U73122 and pertussis toxin (PTX). We found that C5a-induced, time-dependent (1) ERK1/2 phosphorylation was markedly diminished by PTX, U73122, P13K inhibitors wortmannin and LY294002 and ERK1/2 inhibitor PD98059; (2) Akt phosphorylation was also attenuated by the above inhibitors except PD98059; (3) p38 MAPK phosphorylation was only affected by PTX. Furthermore, C5a also stimulated PLCbeta(2) membrane translocation in a time-dependent manner that occurred early prior to Akt phosphorylation and could be abolished only by PTX and U73122. These results suggest that C5a, through the activation of PTX-sensitive G protein, to differentially stimulate ERK1/2 and p38 MAPK phosphorylation and evoke cell migration. That is, ERK1/2 but not p38 MAPK phosphorylation is down stream of P13K/Akt and modulated by PLC. Additionally, beta(2) isoform may be one of the participates in C5a signal and acts more upstream of P13K/Akt.     

Isolation of salicin derivatives from Homalium cochinchinensis and their antiviral activities

The chemical constituents of Homalium cochinchinensis were examined. From the root bark, in addition to the previously reported cochinolide and its beta-glucopyranoside, cochinchiside A (1) and tremulacinol (4) were isolated together with three known compounds [benzoic acid, tremulacin (2), and tremuloidin (3)]. From the leaves, cochinchiside B (5) was isolated as new compound. The structures of the new compounds (1, 4, 5) were determined by spectroscopic and/or chemical methods. Antiviral testing of compounds 2-5 against HSV-1 and HSV-2 showed that tremulacin (2) and cochinchiside B (5) were weakly active. Tremulacin (2) was also weakly active against HIV-1.     

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50,000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8+/-0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50,000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.     

Restaging of recurrent cervical carcinoma with dual-phase [18F]fluoro-2-deoxy-D-glucose positron emission tomography

BACKGROUND: The clinical value of positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) for primary staging in cervical carcinoma appears to be promising. The authors sought to evaluate the diagnostic efficacy and benefit of PET in restaging cervical carcinoma at the time of first recurrence. METHODS: Forty patients with cervical carcinoma who experienced confirmed treatment failure but who were feasible candidates for curative salvage therapy were enrolled prospectively in the current study. Restaging was performed with PET and with computed tomography and/or magnetic resonance imaging (CT/MRI). Dual-phase PET was performed by adding 3-hour-delayed images to the 40-minute scans. The results of the PET and CT/MRI scans were compared. Lesion status was determined by pathologic findings or by clinical follow-up. The receiver operating characteristic curve method with calculation of area under the curve (AUC) was used to evaluate diagnostic efficacy. The primary endpoint was percent improvement in restaging (with improvement indicated by treatment modification) after PET. The secondary endpoint was 2-year overall survival among study participants compared with comparable previously treated patients who did not undergo disease restaging with PET. RESULTS: Twenty-two patients (55%) had their treatment modified due to PET findings. PET was significantly superior to CT/MRI (sensitivity: 92% vs. 60%; AUC: 0.962 vs. 0.771; P<0.0001) in identifying metastatic lesions. For individuals receiving primary surgery, a significantly better 2-year overall survival rate was observed among study participants compared with patients who underwent disease restaging without PET (HR, 0.21 [95% confidence interval, 0.05-0.83]; P=0.020). CONCLUSIONS: Dual-phase FDG-PET is superior to CT/MRI in the restaging of recurrent cervical carcinoma. Restaging with PET provides benefit by allowing the physician to offer optimal management of recurrent cervical carcinoma.     

Synergy between anti-endoglin (CD105) monoclonal antibodies and TGF-beta in suppression of growth of human endothelial cells

Endoglin (CD105) is a proliferation-associated cell membrane antigen of endothelial cells and strongly expressed in the angiogenic vasculature of solid tumors. Endoglin is essential for angiogenesis/vascular development and an ancillary transforming growth factor beta (TGF-beta) receptor. Certain anti-endoglin monoclonal antibodies (mAbs), termed SN6 series mAbs, inhibited angiogenesis, tumor growth and metastasis in mice. We investigated the mechanisms by which anti-endoglin mAbs suppress growth of proliferating endothelial cells. We found that 4 SN6 series mAbs suppressed growth of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner in the absence of any effector cells or complement. Significant differences in the growth suppression between the 4 anti-endoglin mAbs defining different epitopes were observed. These differences were not determined by antigen-binding avidities of the mAbs. Combination of TGF-beta1 and each of the 4 anti-endoglin mAbs exerted synergistic growth suppression of HUVECs. Binding of anti-endoglin mAbs to endoglin-expressing cells did not block the subsequent binding of TGF-beta1. Conversely, preincubation of HUVECs with TGF-beta1 did not change cell surface expression of endoglin. The present results suggest that direct suppression of the endothelial cell growth by SN6 series mAbs is one of the underlying mechanisms by which anti-endoglin mAbs exert antiangiogenic and tumor-suppressive activity in vivo. The results further suggest that TGF-beta1 plays an important role in the in vivo antiangiogenic efficacy of anti-endoglin mAbs by synergistically enhancing the activity of these mAbs. Further studies of the present novel findings may provide valuable information about the functional roles of endoglin and anti-endoglin mAbs in the TGF-beta-mediated cell regulation.     

Gender difference in human papillomarvirus infection for non-small cell lung cancer in Taiwan

Our previous reports have indicated that high risk human papillomarvirus (HPV) 16/18 were much more frequently detected in lung tumors of female patients as compared to that of male patients and HPV 16/18 in lung tumors were evolutionally correlated with those in blood circulation. In the other hand, it is well known that HPV 6/11 are frequently associated with upper aerodigestive and respiratory diseases. HPV 6/11 DNA were detected in lung tumors by nested PCR and in situ hybridization to investigate if any difference in prevalent types of HPV exists between genders. Our data showed that HPV 6 infection was detected in 28.4% (40 of 141) lung tumors, which was significantly higher than that in non-cancer controls (1.7%, 1 of 60; P < 0.0001), however, such high prevalence was not observed for HPV 11. Among studied clinico-pathological parameters, HPV 6 infection was significantly related with gender (P = 0.002) and smoking status (P = 0.014). After being stratified by gender and smoking status, HPV 6 infection rate in lung tumors of non-smoking male patients was much higher than that in non-smoking female patients (33.3% versus 11.1%; P = 0.023), but no difference between smoking and non-smoking male patients (38.1% versus 33.3%). With adjustments for age, tumor type, and tumor stage, smoking male lung cancer patients had a much higher OR value (OR, 7.35; 95%CI, 2.11-25.58) for HPV 6 infection compared with 3.93 (95% CI, 1.17-13.12) of non-smoking male patients. Moreover, a higher prevalence of HPV 6 was detected in lung tumors of smoking male patients with early tumor stage than those with advanced stages (P = 0.008), but not in non-smoking male and female patients. A higher prevalence of HPV 6 in male lung cancer patients, as compared with female lung cancer patients, indicating not only different HPV infection routes for different genders, but also that HPV 6 infections may act as a prospective early risk marker of lung cancer for smoking male patients in Taiwan.     

Clear cell and non-clear cell hepatocellular carcinoma: a case report and literature review

Clear cell hepatocellular carcinoma (HCC) is an uncommon variant of HCC. It is considered to have a better prognosis than non-clear cell HCC, but recent large studies show that there is some controversy. DNA image cytometry reveals diploid and non-diploid DNA content tumors that have different pleomorphisms and mitosis corresponding to different prognoses. Clear cell HCC is classified as focal or diffuse. Herein, we report a rare case of a 61-year-old male with two adjacent hyper- and hypoechoic hepatic nodules and an alpha-fetoprotein concentration of 6,370 ng/mL. Pathologic examination of a specimen obtained during wedge hepatectomy showed both clear cell and non-clear cell HCC. Bone metastasis was later found. We suggest that a patient with clear cell HCC should be followed up closely after complete resection.     

Epidermal growth factor expression in middle ear cholesteatoma

Middle ear cholesteatoma is destructive to auditory ossicles and temporal bone, and treatment usually requires surgical removal of all epithelial content. Epidermal growth factor (EGF) can stimulate the growth and differentiation of a variety of mammalian cells, including epithelial cells. Our study used the avidin-biotin complex technique to evaluate the expression of EGF in 40 cases of middle ear cholesteatoma (active cholesteatoma, 31 cases; inactive cholesteatoma, 9 cases) and 34 normal postauricular skin samples. In middle ear cholesteatoma, EGF was expressed in squamous epithelium in 21 cases (53%), fibroblasts in two cases (5%), and cholesteatoma endothelium in two cases (5%). In normal postauricular skin, EGF was expressed in squamous epithelium in 14 samples (41%), fibroblasts in one sample (3%), and endothelium in none. No statistical difference in EGF expression was found between cholesteatoma and normal postauricular skin samples. These results show that the distribution of EGF in middle ear cholesteatoma is not deranged and that the progression of cholesteatoma might be induced by the release of factors from the cholesteatoma matrix via autocrine stimulation, or by inflammatory cells of the subepithelial tissue through paracrine stimulation, or in both of these ways.