Intraarterial chemotherapy as the first-line therapy in penile cancer.

BACKGROUND: Limited literature on the role of intraarterial chemotherapy as first-line therapy for penile squamous cell carcinoma is available. METHODS: From 2005 to 2013, a total of 12 patients with various stages of penile squamous cell carcinoma received intraarterial chemotherapy. The chemotherapeutic agents used were methotrexate, mitomycin C, bleomycin, cisplatin, and 5-fluorouracil. Surgery was followed by the tumour responses. RESULTS: An objective tumour response was noted in 10 of 12 patients (83%, 4 complete responders and 6 partial responders). In node-negative patients (n=7), the response rate was 100% (4 complete responders and 3 partial responders). Even in advanced penile squamous cell carcinoma with nodal invasion, a response rate of 60% could be achieved. Grade 2 anorexia was the most frequent chemotherapy-related toxicity and no toxic death was noted. Recurrence-free survival was significantly better in patients without lymph node invasion (log-rank test, P=0.041). CONCLUSIONS: Neoadjuvant intraarterial chemotherapy displayed excellent responses for penile squamous cell carcinoma. This therapy could effectively shrink the tumour burden or even achieve complete response before surgery. It could be used as first-line strategy for penile cancer treatment because of low toxicity.

Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients.

Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.

Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-beta1 and cyclooxygenase-2.

Pulmonary fibrosis is a severe complication associated with bis-chloronitrosourea (BCNU) therapy. However, the pathogenetic mechanism has never been well investigated. We report here a 26-year-old female with diffuse large B-cell lymphoma who died of severe pulmonary fibrosis 81 days after the administration of high-dose BCNU (600 mg/m2). Thoracoscopic wedge resection of left upper lung performed 10 days before patient's death showed severe pulmonary fibrosis with prominent hyperplasia of alveolar macrophages and type II pneumocytes. We further used immunohistochemistry (IHC) to examine the relative role of platelet-derived growth factor-B (PDGF-B), insulin-like growth factor I (IGF-I), transforming growth factor-beta1 (TGF-beta1) and cyclooxygenase-2 (COX-2) in the pathogenesis of BCNU-related pulmonary fibrosis. Strong expressions of PDGF-B and IGF-1 on alveolar macrophages and type II pneumocytes were clearly demonstrated, but in contrast, the expressions of TGF-beta1 and COX-2 were almost undetectable. In conclusion, pulmonary fibrosis can develop early and progress rapidly after the administration of high-dose BCNU. The markedly increased expression of fibrogenic factors PDGF-B and IGF-1 on hyperplastic alveolar macrophages and hyperplastic type II pneumocytes may play an important role in the fibrogenesis of this disease. These novel findings may offer specific therapeutic targets in the treatment of BCNU-associated pulmonary fibrosis.

Weekly gemcitabine plus 24-h infusion of high-dose 5-fluorouracil/leucovorin for locally advanced or metastatic carcinoma of the biliary tract.

Both gemcitabine and weekly 24-h infusion of high-dose 5-fluorouracil/leucovorin (HDFL) have shown promising antitumour activity for patients with locally advanced or metastatic carcinoma of the biliary tract (CBT). From April 1999 through December 2002, 30 patients with inoperable CBT were treated with gemcitabine 800 mg m(-2), intravenous infusion for 30 min, followed by 5-FU, 2000 mg m(-2) and leucovorin, 300 mg m(-2), intravenous infusion for 24 h, on day 1, 8 and 15, every 4 weeks. A total of 166 cycles were given (median of four cycles per patient, range 1-24 cycles). Response was evaluable in 28 patients and toxicity in 29 patients. Partial response was obtained in six patients, stable disease in 13, while progressive disease occurred in nine. The objective response rate was 21.4% (95% CI: 5.2-37.6%). The most common grade 3 or 4 toxicity was infection (nine patients). Other types of grade 3 or 4 toxicity included leucopenia (four patients), thrombocytopenia (three patients), anaemia (three patients), nausea/vomiting (two patients) and elevation of liver transaminases (three patients). As of 30 September 2003, the median progression-free survival was 3.7 months (95% CI: 2.8-4.6 months) and the median overall survival was 4.7 months (95% CI: 0.8-8.6 months). Our data suggest that weekly gemcitabine plus HDFL is modestly active with acceptable treatment-related toxicity for patients with advanced CBT.

Anti-inflammatory effects of the partially purified extract of radix Stephaniae tetrandrae: comparative studies of its active principles tetrandrine and fangchinoline on human polymorphonuclear leukocyte functions.

We hypothesized that prevention of neutrophil from activation may underlie the myocardial protective effect of the specially processed extract of radix Stephaniae tetrandrae (SPRST). Inflammatory responses in isolated peripheral human neutrophils were studied in the presence or absence of SPRST. SPRST (1-10 microg/ml) concentration-dependently prevented N-formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene B(4) (LTB(4))-induced neutrophil adhesion and transmigration. Comparable results were also observed in neutrophils pretreated with fangchinoline (Fan) or tetrandrine (Tet), two active components in SPRST. It has been reported that neutrophil adhesion/transmigration is mainly Mac-1 (CD11b/CD18)-dependent and could be modulated by reactive oxygen species (ROS) production. SPRST, Tet, and Fan diminished fMLP- or LTB4-induced Mac-1 up-regulation and ROS production. SPRST, Fan, Tet, and verapamil impaired fMLP-induced rapid intracellular alkalization, an essential mechanism for neutrophil ROS production, and [Ca(2+)](i) increment, suggesting that a calcium dependent pathway might be involved. Direct G protein activation by AlF(4)(-) also triggered [Ca(2+)](i) increment and adhesion that could be abolished by pertussis toxin and were partially reversed by SPRST, Fan, and Tet. These results reveal that inhibition of neutrophil adhesion and transmigration may account for SPRST's myocardial protective effect. This effect of SPRST may be mediated by component(s) in addition to Tet and Fan because combination of 0.1 microg/ml of Tet and Fan did not mimic the effect of SPRST. We conclude that SPRST exerts anti-inflammatory effects by interfering with ROS production and Ca(2+) influx through G protein modulation to prevent Mac-1 up-regulation in neutrophil activation.

Taxane diterpenoids from the stem bark of Taxus mairei.

Three new 11(15-->1)-abeo-taxanes, taxumairols U-W (1-3), have been isolated from extracts of the stem bark of Formosan Taxus mairei. The structures of 1-3 were identified as 5alpha,7beta,9alpha,13alpha,20-pentaacetoxy-2alpha,10beta,15-trihydroxy-11(15-->1)-abeo-taxene, 5alpha,7beta,9alpha,20-tetraacetoxy-2alpha,10beta,13alpha,15-tetrahydroxy-11(15-->1)-abeo-taxene, and 2alpha,4alpha,7beta,10beta-tetraacetoxy-5beta,20-epoxy-9alpha,13alpha,15-trihydroxy-11(15-->1)-abeo-taxene, respectively, on the basis of 2D NMR techniques including COSY, HSQC, HMBC, and NOESY experiments as well as chemical reactions of compounds 1-3 to give 4 (5alpha,7beta,9alpha,10beta,13alpha,20-hexaacetoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene) and 5 (4alpha,7beta,10beta-triacetoxy-9alpha,13alpha-dibenzoxy-5beta,20-epoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene), which are also novel taxane derivatives. Taxumairols U (1) and V (2) exhibited significant cytotoxicities against human hepatoma tumor cells, while taxumairol W (3) was inactive.

Taxane diterpenoids from seeds of Taxus mairei.

A new 2(3-->20) abeotaxane, taxumairone A (1), and a new cis-p-coumaroyl myo-inositol have been isolated from the seeds of Taxus mairei in addition to taxin B (2), taxinine A, taxuspine X, decinnamoyltaxinine E, 5alpha-cinnamoyloxy-9alpha,10beta,13alpha- triacetoxy-taxa-4(20)11-diene and 5alpha-cinnamoyloxy-2alpha,9alpha,10beta,+ ++13alpha-tetraacetoxy-taxa-4(20)11-diene. The structure of 1 was determined by 2D-NMR spectral analysis and chemical correlation with taxin B (2). Compound 1 exhibited potent cytotoxicity against human colon carcinoma cells with an ED50 of 0.1 microg/ml.

Suppression of rat neutrophil reactive oxygen species production and adhesion by the diterpenoid lactone andrographolide.

The present study was to examine whether andrographolide, a diterpenoid lactone isolated from the anti-inflammatory herbal medicine Andrographis paniculata (Burm. f.) Nees. (Acanthaceae), has the ability to prevent phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion by rat neutrophils. Results demonstrated that PMA (100 ng/ml) induced rapid accumulation of H2O2 and O2. in neutrophils within 30 minutes. Andrographolide (0.1 to 10 microM) pretreatment (10 min, 37 degrees C) significantly attenuated the accumulation of these two oxygen radical metabolites. Administration of andrographolide also significantly prevented fMLP-induced neutrophil adhesion. These data suggest that preventing ROS production and neutrophils adhesion may confer andrographolide the ability to be an anti-inflammatory drug.

New taxanes with an opened oxetane ring from the roots of Taxus mairei.

Two novel taxoids, taxumairols N (1) and O (2), have been isolated from extracts of the roots of Taxus mairei. The structures of 1 and 2 were identified as 7beta,9alpha,10beta,13alpha-tetraacetoxy-2alp ha, 4alpha,5alpha,20-tetrahydroxytax-11-ene and 7beta,9alpha,10beta, 13alpha-tetraacetoxy-1beta,2alpha,4alpha,5alp ha, 20-pentahydroxytax-11-ene on the basis of 1D and 2D NMR techniques including COSY, HMQC, HMBC, and NOESY experiments.

A novel cytotoxic C-methylated biflavone from the stem of Cephalotaxus wilsoniana.

Bioassay-directed fractionation of an ethanolic extract of Cephalotaxus wilsoniana has resulted in the isolation of a novel C-methylated biflavone, taiwanhomoflavone-A (1). Its structure was elucidated on the basis of spectroscopic analysis. Taiwanhomoflavone-A is cytotoxic with ED50 values of 3.4, 1.0, 2.0 and 2.5 microg/ml, respectively, against KB epidermoid carcinoma of nasopharynx, COLO-205 colon carcinoma, Hepa-3B hepatoma, and Hela cervix tumor cells.

Taxumairol M: a new bicyclic taxoid from seeds of Taxus mairei.

In addition to taxol A (1), 10-deacetyltaxol A (2), 10-deacetyl-7-epi-taxol A (3), 10-deacetylbaccatin III (5), taxuspine Z, taxezopidine G, 5 alpha-cinnamoyloxy-9 alpha,10 beta,13 alpha-triacetoxytaxa-4(20)11-diene, taxinine J, and taxinine M, a new bicyclic taxoid named taxumairol M (4), has been isolated from the seeds of Taxus mairei. The structure of 4 was determined on the basis of spectral analysis.

Taxane diterpenoids from the seeds of Chinese yew Taxus chinensis.

The taxoid chinentaxunine has been isolated from the seeds of Chinese yew Taxus chinensis, and its structure determined on the basis of spectral and chemical methods. In addition, the known taxol C, paclitaxel, 10-deacetyl taxol A, 10-deacetyl-7-epitaxol, 10-deacetyl-10-oxo-7-epi-taxol, taxinine M, taxchinin A, 10-deacetyl taxinine B and taxuspine X were also isolated and identified from this source.

A new taxane diterpenoid from Taxus mairei.

A new 11(15-->1)-abeotaxane diterpene, taxumairol K (1), has been isolated from the ethanolic extract of the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y. Hu. The structure of 1 was determined as 9alpha-(benzoyloxy)-2alpha,4alpha- diacetoxy-5beta ,20-epoxy-1beta, 7beta,10beta,13alpha-tetrahydroxy-11(15-->1)-abeota xane on the basis of spectral analysis. Taxumairol K (1) exhibited mild cytotoxicity against HeLa tumor cells.

Magnolol inhibits Mac-1 (CD11b/CD18)-dependent neutrophil adhesion: relationship with its antioxidant effect.

Magnolol, a phenolic compound isolated from a Chinese herbal drug, Magnolia officinalis, has been shown to protect rat heart from ischemia/reperfusion injury. Neutrophil adhesion plays a crucial process during this inflammatory response. To evaluate whether magnolol prevents ischemia/reperfusion injury by inhibiting neutrophil adhesion, we determined whether magnolol can inhibit adhesion of phorbol-12-myristate-13-acetate (PMA)-activated human neutrophils to a fibrinogen-coated surface in a dose-dependent manner. Using flow cytometric analysis, we observed that magnolol pretreatment (10 min at 37 degrees C) diminished PMA (100 ng/ml)-induced Mac-1 upregulation. PMA also induced rapid intracellular accumulation of superoxide (O2-.) and hydrogen peroxide (H2O2) in neutrophils; magnolol pretreatment attenuated the accumulation of these two substances. Inhibition of reactive oxygen species by superoxide dismutase and/or catalase, which decompose O2-. and H2O2, respectively, also abolished Mac-1 upregulation and neutrophil adhesion. We conclude that magnolol inhibits neutrophil adhesion and that this can account for its anti-ischemia/reperfusion injury effect. We propose that the inhibitory effect of magnolol on neutrophil adhesion to the extracellular matrix is mediated, at least in part, by inhibition of the accumulation of reactive oxygen species, which in turn suppresses the upregulation of Mac-1 that is essential for neutrophil adhesion.

[Therapeutic effect of shuxuening combining neuroleptics for the treatment of chronic schizophrenia--a double blind study].

OBJECTIVE: To assess the therapeutic effect of Shuxuening (SXN), the extractum of Ginkgo biloba761 (EGb761) in treating chronic schizophrenia. METHODS: A double-blind, placebo-controlled multi-center research on the treatment of chronic schizophrenics with SXN was used. Five hundred and forty-five patients were randomly divided into either SXN group or the control group. Patients in the former group received SXN 120 mg three times daily. Patients in both groups received their maintenance neuroleptics throughout the 16-week research treatment. RESULTS: The patients' rating scores of brief psychiatric rating scale (BPRS) and Scale for the Assessment of Negative Symptoms reduced much greater in SXN group than those in the control group from the sixth week of treatment (P < 0.01). The effect of SXN for BPRS factors of retardation and thought disturbance was better than that of the control. SXN presented a better therapeutic effect for chronic schizophrenics than the control when rated with traditional global rating method as well, in which 44.98% marked improvement was obtained in SXN group compared to 20.98% in the control group. CONCLUSION: SXN combining neuroleptics, was an effective medicine for chronic schizophrenics. Moreover, it appeared few side-effects within the recommended dose range.

Zhankuic acid F: a new metabolite from a formosan fungus Antrodia cinnamomea.

Zhankuic acid F (1), a new steroid acid, was isolated from the fruit bodies of Antrodia cinnamomea Chang & Chou, sp. nov. (Polyporaceae). The structure of 1 was elucidated by detailed analysis of 1D- and 2D-NMR spectra. Compound 1 appeared as a major product from the microbial transformation (Mucor racemosus) of zhankuic acid A (2).

Taxane diterpenes from Taxus mairei.

In addition to 7-O-deacetyl-1 beta-hydroxybaccatin I and 9-O-deacetyl-1 beta-hydroxybaccatin I, a new taxane taxumairol F has been isolated from the ethanolic extracts of the roots of Taxus mairei. Their structures were determined on the basis of spectral evidence and chemical correlation with 1-beta-hydroxybaccatin I.

New secoiridoid glucosides from Jasminum lanceolarium.

Two new secoiridoid glucosides, the trans-P-coumaroyl and trans-feruloyl esters of 10-hydroxyoleoside, jaslanceosides A (2) and B (3), were isolated from the leaves and stems of Jasminum lanceolarium (Oleaceae) in addition to jasminoside (1) and 10-hydroxyoleoside dimethyl ester (8). The structures of these compounds have been elucidated on the basis of spectral and chemical methods.

New taxane diterpenoids from the roots of Taxus mairei.

Two new taxoids, taxumairols A (1) and B (2), have been isolated from extracts of the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y. Hu. The structures of 1 and 2 were identified as 5 alpha, 7 beta, 9 alpha, 10 beta, 13 alpha-pentaacetoxy-20-(benzoyloxy)- 2 alpha, 4 alpha-dihydroxytax-11-ene and 2 alpha, 5 alpha, 10 beta,-13 alpha-tetraacetoxy-1 beta, 7 beta, 9 alpha-trihydroxy-4 beta,20-epoxytax-11-ene, primarily on the basis of 1D- and 2D-NMR techniques including DEPT, COSY, and HMBC experiments, as well as chemical correlation with known compounds. Taxumairol A (1) exhibited significant cytotoxicities against murine P-388 and human KB-16, A-549, and HT-29 tumor cell lines.