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Decavanadate compounds were described to be involved in a variety of biological activities and responses such as anti-virus, anti-bacterial and anticancer. While the mechanisms of action of the antiviral and anti-bacterial activities are better understood, the same does not go for the anti-tumour activity. Nevertheless, the inhibition of tumour proliferation seems to impact certain enzymes such as alkaline phosphatase, ecto-nucleotidases or P-type ATPases. In the present report, several studies are described, in a way to explain the increasing interest of these polyoxometalate in cancer therapy. The detailed knowledge of the molecular basis of decavanadate–proteins and cellular interactions allows to better understand the processes associated with the anticancer applications, not only for decavanadate but as well for other polyoxometalates (POMs).

Cynanchum wallichii Wight, is a traditional Chinese medicine herb, which is rich in saponins and has varieties of pharmacological activities. In this study, a standardized C. wallichii extract was established and the anti-tumor activity of the total saponins was evaluated by MTT assay. The extraction conditions of the standardized extract was optimized using response surface methodology. The experimental value was in good agreement (the yield 4.28%) with predicted values. The total saponins of the extract showed significant anti-tumor activity against three human tumor cell lines (A549, HepG2 and MCF-7), especially for MCF-7 (IC50. 67.63 μg/mL) cells in vitro.

Cediranib (AZD2171) is a highly potent inhibitor of all three vascular endothelial growth factor receptors. The aim of this preclinical study was to examine the effect of combining cediranib with mechanistically distinct anti-tumour therapies.Cediranib (1.5 or 3 mg/kg/day) was evaluated alone and in combination with either gefitinib, imatinib, ZD6126, saracatinib, selumetinib, bevacizumab, 5-fluorouracil (5-FU), docetaxel, oxaliplatin, gemcitabine, pemetrexed, irinotecan or cisplatin in human tumour xenograft models. Anti-tumour activity was measured by assessing the change in tumour volume following treatment compared with vehicle-treated time-matched controls.In all cases, the combination regimens, at tolerated doses and schedules, inhibited tumour growth to a greater extent than the corresponding monotherapy treatments. Compared with cediranib alone, statistically significant enhancements in anti-tumour activity were observed with all combination regimens. Notably, after 14 days of treatment, the combination of cediranib with ZD6126 induced substantial tumour regression (60 % compared with pre-treatment volume), whilst treatment with each agent alone led only to partial growth inhibition. A combination of cediranib with gefitinib also induced tumour regressions, and cediranib combined with either gemcitabine or irinotecan was found to inhibit tumour growth profoundly (by 99 and 98 %, respectively).Combining cediranib with selected cytotoxic or targeted agents proved efficacious in a range of human tumour xenograft models.

Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy.

The high edible oil content of Xanthoceras sorbifolia Bunge seeds contributes to its economic value. In this study, we analysed the barrigenol-like triterpenoids derived from X. sorbifolia husks. We also identified anti-tumour agents that could enhance the health benefits and medicinal value of X. sorbifolia. We isolated 10 barrigenol triterpenoids, including six new compounds (1-6) and four known compounds (7-10). New compounds 3 and 5 showed significant inhibitory activity against the proliferation of three human tumour cell lines, namely, HepG2, HCT-116 and U87-MG. We determined the relationship between the structures and inhibitory activity of 25 barrigenol triterpenoids and 15 penta-cyclic triterpenoids through analysis of three-dimensional quantitative structure activity relationships (3D-QSAR). The isolation of novel barrigenol derivatives with anti-tumour activity from X. sorbifolia implied that husks of this plant may be a good source of anti-tumour agents.

High yielding and diastereoselective conjugate addition reactions of a (−)-quinic acid derived enone have provided access to a small library of hybrid analogues of the anti-tumour natural products antheminone A and COTC. The novel compounds were assessed for their antiproliferative activities towards the A549 non-small-cell lung cancer cell line revealing some useful structure-activity relationships.

Oridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis‐ and autophagy‐inducing activity and relevant molecular mechanisms in cancer therapy. Apoptosis is a well known type of cell death, whereas autophagy can play either pro‐survival or pro‐death roles in cancer cells. Accumulating evidence has recently revealed relationships between apoptosis and autophagy induced by oridonin; however, molecular mechanisms behind them remain to be discovered. In this review, we focus on highlighting updated research on oridonin‐induced cell death signalling pathways implicated in apoptosis and autophagy, in many types of cancer. In addition, we further discuss cross‐talk between apoptosis and autophagy induced by oridonin, in cancer. Taken together, these findings open new perspectives for further exploring oridonin as a potential anti‐tumour agent targeting apoptosis and autophagy, in future anti‐cancer therapeutics.

The purpose of this study was to investigate the effect of paclitaxel in combination with 20(s)-ginsenoside Rg3 on its anti-tumour effect in nude mice. In the Caco-2 transport assay, the apparent permeability from the apical side to the basal side (P(app)) (A-B) and P(app) (B-A) of paclitaxel were measured when co-incubated with different concentrations of 20(s)-ginsenoside Rg3. The results indicated that the penetration of paclitaxel through the Caco-2 monolayer from the apical side to the basal side was facilitated by 20(s)-ginsenoside Rg3 in a concentration-dependent manner. Meanwhile, 20(s)-ginsenoside Rg3 inhibited P-glycoprotein (P-gp), and the maximum inhibition was achieved at 80 µM (p < 0.05). The pharmacokinetic parameters of paclitaxel after oral co-administration of paclitaxel (40 mg/kg) with various doses of 20(s)-ginsenoside Rg3 in rats were investigated by an in vivo pharmacokinetic experiment. The results showed that the AUC of paclitaxel co-administered with 20(s)-ginsenoside Rg3 was significantly higher (p < 0.001 at 10 mg/kg) compared with the control. The relative bioavailability (RB) % of paclitaxel with 20(s)-ginsenoside Rg3 was 3.4-fold (10 mg/kg) higher than that of the control. The effect of paclitaxel orally co-administered with 20(s)-ginsenoside Rg3 against human tumour MCF-7 xenografts in nude mice was also evaluated. Paclitaxel (20 mg/kg) co-administered with 20(s)-ginsenoside Rg3 (10 mg/kg) exhibited an effective anti-tumour activity with the relative tumor growth rate (T/C) values of 39.36% (p

Objectives The aim of this study was to investigate the pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin submicron emulsions (HCPT-SEs). Methods HCPT-SEs or HCPT injection (HCPT-I) was administered intravenously into the tail vein of rats or S180 tumour-bearing mice. Key findings HCPT-SEs increased the plasma concentration of HCPT compared with HCPT-I at all time points. The AUC0-∞, elimination half-life and mean residence time of anionic submicron emulsions containing HCPT (HCPT-ASEs) and cationic submicron emulsions containing HCPT (HCPT-CSEs) were significantly greater than those of HCPT-I (P < 0.01). Especially, a prolonged elimination half-life was found for HCPT-CSEs. HCPT-CSEs and HCPT-ASEs resulted in a 7.9-fold and 3.1-fold increase in AUC0-6h of tumour compared with HCPT-I, respectively. The targeting efficiency (Te) of HCPT-ASEs and HCPT-CSEs indicated their selectivity to tumour and the Te of HCPT-CSEs was significantly higher than that of HCPT-ASEs (P < 0.01). The anti-tumour effect studies showed that HCPT-SEs improved the therapeutic efficiency of HCPT compared with HCPT-I. The percentage of tumour growth suppression rate of mice treated with HCPT-CSEs (2.0 mg HCPT eq./kg) increased 2.1 fold compared with that of HCPT-I. Conclusions Submicron emulsions can alter the pharmacokinetic characteristics and tissue distribution of HCPT, and enhance tumour targeting and anti-tumour activity.

OLIG2 is a protein transcription factor that is expressed exclusively in progenitor cells in the brain and spinal cord during development. Typically, OLIG2 is not active in the adult brain and is not found outside the central nervous system; however, it is re-expressed in most patients with high-grade glioma (HGG). The expression of OLIG2 potentially drives the growth, invasiveness, and resistance to radiation of HGG cells and tumours in animal models. CT-179 is a small molecule (M.W. 397) that, on the basis of homology modelling studies, is a putative disruptor of OLIG2 homodimerization. We found that, at low nanomolar concentrations, CT-179 profoundly inhibited the growth of, and induced apoptosis in, a range of patient-derived HGG cell lines. Approximately half of the HGG cell lines showed substantial degradation of OLIG2 protein, and this was associated with arrest of the cells in the G2/M phase of the cell cycle. We are currently exploring whether this leads to mitotic catastrophe. Additionally, CT-179 caused significant downregulation of receptor tyrosine kinases that are associated with HGG tumorigenicity, including epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR). Orally administered CT-179 (20 mg/kg) crossed the blood-brain barrier of intact mice and reached levels sufficient to inhibit HGG cells. Indeed, the growth of established orthotopic HGG xenografts in mice was significantly inhibited by orally or intraperitoneally administered CT-179, leading to increased survival. CT-179 is one of the few small molecules that has been identified to directly inhibit the function of a transcription factor. Our experiments showing the profound anti-tumour activity of CT-179 in HGG models provide the impetus needed for moving this molecule into the clinic as a novel therapy for patients with HGG.

Based on the logistic growth law for a tumour derived from enzymatic dynamics, we address from a physical point of view the phenomena of synergism, additivity and antagonism in an avascular anti-tumour system regulated externally by dual coupling periodic interventions, and propose a theoretical model to simulate the combinational administration of chemotherapy and immunotherapy. The in silico results of our modelling approach reveal that the tumour population density of an anti-tumour system, which is subject to the combinational attack of chemotherapeutical as well as immune intervention, depends on four parameters as below: the therapy intensities D, the coupling intensity I, the coupling coherence R and the phase-shifts Φ between two combinational interventions. In relation to the intensity and nature (synergism, additivity and antagonism) of coupling as well as the phase-shift between two therapeutic interventions, the administration sequence of two periodic interventions makes a difference to the curative efficacy of an anti-tumour system. The isobologram established from our model maintains a considerable consistency with that of the well-established Loewe Additivity model (Tallarida, Pharmacology 319(1):1-7, 2006). Our study discloses the general dynamic feature of an anti-tumour system regulated by two periodic coupling interventions, and the results may serve as a supplement to previous models of drug administration in combination and provide a type of heuristic approach for preclinical pharmacokinetic investigation.

We present the case of a 70-year-old man with stage IV lung adenocarcinoma. He was treated with pembrolizumab, a programmed cell death-1 (PD-1) inhibitor, as a first-line therapy. After six cycles of pembrolizumab, he suddenly developed cardiac tamponade. With the exception of newly massive malignant pericardial effusion, the other malignant lesions improved. Pembrolizumab was continued and the patient has shown a durable response for two years. This is the unique case of late-onset pericaridial effusion with pembrolizumab, showed discrepant anti-tumour effects. A proper assessment is crucial to ensure favourable clinical outcomes in patients treated with PD-1 inhibitor.

The bark of Wikstroemia indica is rich in daphnoretin, which has strong antiviral and anti-tumour activities. In order to optimise the extraction conditions of daphnoretin from the bark of W. indica, various extraction parameters were chosen to identify their effects on daphnoretin extraction. Response surface methodology (RSM) was applied to obtain the optimal combination of these parameters. Results showed that the optimisation conditions for daphnoretin extraction were: ethanol concentration 67.44%, extraction time 49.44 min, temperature 60.19 °C and liquid–solid ratio 23.49:1. The maximum extraction of daphnoretin obtained experimentally was 2.18‰. The mathematical model developed was found to fit well with the experimental data. Further, four kinds of human cancer cell lines, HeLa, A549, CNE and HEp-2, were tested in vitro to explore the anti-tumour spectrum of daphnoretin. It was found for the first time that daphnoretin showed significant inhibition on the proliferation of CNE and HeLa cells.

In the present study, extracts of CHCl(3), n-BuOH and water of Lomatogonium carinthiacum were tested for their possible anticancer effects on human lung adenocarcinoma A549 cell line, human erythroleukaemia K562 cell line and human cervical carcinoma HeLa cell line. The inhibitory effect of the extracts on cell proliferation was assessed by MTT colourimetric assay in vitro. A high-performance liquid chromatography-electrospray-mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts. According to HPLC-EIS-MS/MS data, the chemical structures of 21 constituents of L. carinthiacum were identified on-line without time-consuming isolation. The L. carinthiacum extracts showed inhibitory effects on the abovementioned cell lines. Extracts of CHCl(3) were found to be the most inhibitory, with IC(50) values of 0.13, 0.75 and 0.60 µg mL(-1) on A549, K562 and HeLa, respectively. According to the IC(50) values, the order of sensitivity of the cell lines was A549 > HeLa > K562 and the inhibitory effects to the cell lines of these extracts were in the order CHCl(3) extract > water extract > n-BuOH, as xanthones > iridoids and secoiridoids > flavonols. The present study showed inhibitory activity of L. carinthiacum extracts on tumour cells.

Objective: Bauhinia phoenicea Wight and Arn. is a medicinal plant endemic to Southern Western Ghats. In the traditional systems of medicine, it is using against various ailments including some oxidative disorders. Detailed studies on the pharmacological activities of this plant are not yet reported. Hence, this paper aimed to prove the efficacy of this plant as a natural antioxidant source.Methods: The sequential extracts of the dried leaf powder were assayed for an antioxidant property using 2,2 diphenyl 1-picrylhydrazyl free radical scavenging assay, in vitro cytotoxicity of the extracts was screened using Trypan blue exclusion method. The antitumor activity of the selected fractions was studied using ascites tumor affected mice and noted the percentage of increase in lifespan.Results: The free radical scavenging activity of all extracts was increasing with increasing concentration of the drug, the least IC50 value was showed by ethanol fraction (41 μg/ml). The plant drug was not toxic to the normal cells and was highly toxic to tumor cell lines. Maximum in vitro cytotoxicity was observed in chloroform fraction (98% cell death at 100 mg/ml) and the least IC50 value was exhibited by the aqueous fraction (34 mg/ml). Both the aqueous and chloroform fractions increased the lifespan of ascites tumor bearing mice, aqueous fraction in 100 mg/ml concentration shows 71.9% increase in lifespan which is near to the result showed by the commercial anticancer drug cyclophosphamide (72.5%).Conclusion: According to our results, it is concluded that leaf of B. phoenicea has significant antioxidant, cytotoxic, and antitumor properties supporting the folk medicinal use of this species. The further procedures of identification of pharmacological active principles are in progress.

The syntheses of five novel 2-oxyalkyl-cyclohex-2-enones, structurally related to the natural products COTC and antheminone A, are described. The target structures were selected in order to probe the influence of several key structural parameters on in vitro anti-cancer bioactivity. The results of a cytotoxicity bioassay of the compounds against non-small-cell lung cancer cell lines A549 and H460 are reported. The biological data provides useful information, which will help guide the future design of compounds in this class with enhanced anti-cancer activity.

The synthesis and characterisation of fifteen new organotin compounds containing at least two CF3(CF2)5CH2‐CH2 groups bound to tin are described. The activity of six of these compounds towards the murine P388 lymphocytic leukaemia tumour is given. Copyright © 1984 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis and characterization of the RuII complexes, [Ru(N−N)3][CF3SO3]2, where N−N is 4,4′-biimidazole (complex 1a) or 2,2′-dimethyl-4,4′-biimidazole (1b), and the dimethylsulfoxide complexes RuCl2(DMSO)2(N−N) are reported. The air-stable, water-soluble complexes were characterized by elemental analysis, 1H NMR and IR spectroscopies, mass spectrometry, and solution conductivity. Evidence is presented also for the existence of the diruthenium complexes Ru2Cl4(DMSO)4(N−N), but there are insufficient data for elucidation of their structure. The complexes (and cisplatin) were tested against human breast-cancer cells (MDA-MB-435S) using an in vitro MTT assay, a colorimetric determination of cell viability: 1a and 1b exhibit the lowest IC50 values of 18 ± 5 and 36 ± 5 µmol/L, respectively, with cisplatin exhibiting an IC50 value of 35 ± 5 µmol/L. Isolation of DNA from cells treated with a solution of the Ru species showed no evidence of DNA-binding to the metal, although examination of the cells indicated that Ru was being taken up into the cells.

Background: Survivin, a member of the inhibitor of apoptosis protein family, is an attractive target for cancer therapy. We have now investigated the effects of the combination of YM155, a novel small-molecule inhibitor of survivin expression, and platinum compounds (cisplatin and carboplatin) on human non-small cell lung cancer (NSCLC) cell lines. Methods: The anti-cancer efficacy of YM155 in combination with platinum compounds was evaluated on the basis of cell death and progression of tumour xenografts. Platinum compound-induced DNA damage was evaluated by immunofluorescence analysis of histone γ-H2AX. Results: Immunofluorescence analysis of histone γ-H2AX showed that YM155 delayed the repair of double-strand breaks induced in nuclear DNA by platinum compounds. The combination of YM155 and platinum compounds also induced synergistic increases both in the number of apoptotic cells and in the activity of caspase-3. Finally, combination therapy with YM155 and platinum compounds delayed the growth of NSCLC tumour xenografts in nude mice to an extent greater than that apparent with either treatment modality alone. Conclusion: These results suggest that YM155 sensitises tumour cells to platinum compounds both in vitro and in vivo, and that this effect is likely attributable to the inhibition of DNA repair and consequent enhancement of apoptosis.

Used against a variety of tumours, doxorubicin (DOX), causes multiple side-effects in patients, especially in high doses required to control tumour growth. A drug delivery system (DDS) was developed to deliver DOX. Through DOX encapsulation into chitosan DDS, novel DOX microparticles (DMPs) were formed. Multiple optimisation steps produced DMPs which caused tumour cell death. Treatment of mice bearing tumours with DMP decreased tumour growth and spread, with no visible side-effects. There are plans to evaluate this delivery vehicle more closely towards clinical development and testing.

Paclitaxel is a commonly used anticancer drug, but it frequently causes peripheral neuropathy. Neurotropin, a non-protein extract from inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic painful conditions. In the present study, we investigated the effect of neurotropin on the paclitaxel-induced neuropathy in rats. Repeated administration of paclitaxel induced mechanical allodynia, cold hyperalgesia, and motor dysfunction. These neuropathies were mostly reversed by the repeated administration of neurotropin. Furthermore, neurotropin ameliorated the paclitaxel-induced axonal degeneration in cultured PC12 and rat dorsal root ganglion cells, and in rat sciatic nerve. In addition, neurotropin did not affect the microtubule aggregation or anti-tumour effect induced by paclitaxel in the tumour cell lines or tumour cells-implanted mice. These results suggest that neurotropin reverses the paclitaxel-induced neuropathy without affecting anti-tumour activity of paclitaxel, and therefore may be useful for the paclitaxel-induced neuropathy in clinical settings.

SUMMARY In the present study, the ethanolic leaf and bark extract of Wrightia tomentosa were tested forcomparative in vivo antitumour properties against Ehrlich ascites carcinoma (EAC) tumourbearing mice at 100 and 200 mg/kg body weight doses given orally once daily for 16 days. TheEAC mice receiving 100 and 200 mg/kg ethanolic leaf and bark extract showed a dose dependentelevation in tumour – free survival and a highest number of survivors were observed at 200 mg/kg for leaf extract of ethanol, which was considered as an optimum dose for its anti neoplasticaction. The Median survival time for this dose was approximately 44 days when compared with23 days of non-drug treated controls. The results indicate that the administration of leaf extractnot only increased the survival of animals with ascites tumour and reduced packed cell volumeand viable tissue cell count, but also altered many hematological parameters changed duringtumour progression, indicating the potent antitumour nature of leaf extract than the bark extract.Statistical analysis also reveals that the leaf extract showed highly significant anti tumour potency(p < 0.001) when compared with control.Key words: Wrightia tomentosa; Ethanol extract; Leaf, Bark; Ehrlich ascites carcinoma (EAC);antitumour

Syntheses of three novel analogues of the Streptomyces metabolite COTC are described, using the versatile chiral pool starting material, (−)-quinic acid. The results of bioassays of the target compounds against two lung cancer cell lines, A549 and H460, are presented.

This Perspective discusses the feasibility of identifying oncoantigens (proteins required for tumour progression) using mouse models and human mRNA profiling data. Will such oncoantigens make good cancer vaccine targets?

Cervical cancer is the second most common cancer among women in the world. It is still the most common gynaecological cancer worldwide. Plants have remained an important source in the search for no...

During 2003 and 2004, marine pharmacology research directed towards the discovery and development of novel anti-tumour agents was published in 163 peer-reviewed articles. The purpose of this review is to present a structured assessment of the anti-tumour and cytotoxic properties of 150 marine natural products, many of which are novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids and peptides. The organisms yielding these bioactive marine compounds include invertebrate animals, algae, fungi and bacteria. Anti-tumour pharmacological studies were conducted with 31 structurally defined marine natural products in a number of experimental and clinical models that further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human tumour cell lines was reported for 119 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anti-cancer research was sustained by a global collaborative effort, involving researchers from Australia, Austria, Canada, China, Egypt, France, Germany, Italy, Japan, Mexico, the Netherlands, New Zealand, Papua New Guinea, the Philippines, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand and the United States of America (USA). Finally, this 2003-2004 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine anti-tumour agents continued at the same pace as during 1998-2002.

The successful treatment of cancer remains a huge challenge. Consequently, efforts are being made to develop alternative methods of tumour therapy. One of these is the use of live Clostridium species, based on the observation that obligatory anaerobic bacteria specifically colonize the hypoxic and necrotic regions that are present in solid tumours but normally absent in other parts of the body. Although past results have fuelled scepticism about its clinical use, recent promising findings emphasize the potential of Clostridium-directed tumour therapy. These recent developments are reviewed and the reintroduction of this tumour-targeting protein delivery system into clinical settings is discussed.

Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity of chemotherapy, in particular, platinum-based chemotherapy. Finding successful strategies for the targeting of platinum anticancer drugs has therefore been a subject of extensive research. This review paper gives an overview of some of the different approaches that have recently been used in the development of targeted platinum anticancer drugs.

Depot system for local drug delivery using chitosan hydrogel has been developed to enhance the therapeutic efficacy and to prevent the severe side effect in whole body. Thus, we have prepared an injectable chitosan hydrogel containing liposomes to treat cancers clinically. Anionic liposomes incorporated to improve sustained release efficiency within chitosan hydrogel. The chitosan solution containing liposomes was designed to form a hydrogel complex at body temperature. The released behavior of doxorubicin from liposomes in chitosan hydrogel showed sustained-release caused by diffusion of doxorubicin from temperature responsive liposome into chitosan hydrogel. The chitosan hydorgel containing liposomes enhanced the therapeutic potency for the solid tumor in vivo system. Our results indicate that the liposomes in chitosan hydrogel represent a depot system for local drug delivery.

Irinotecan (CPT-11) is an important anticancer agent activated by carboxylesterase (CE). Treatment with CPT-11 may be associated with severe adverse effects, however, so determining the optimal dose would greatly benefit patients. We investigated the relationship between the anti-tumour effects of CPT-11 and CE concentration using bis- p-nitrophenylphosphate (BNPP), a specific inhibitor of CE, in nude mice with xenograft tumours. Initial experiments showed that the optimal dose of CPT-11 was 100 mg/kg. This dose was then used to study the anti-tumour effects of CPT-11 with and without BNPP. A direct correlation was found between the dose of administered BNPP and the growth rate of the tumour, demonstrating that the anti-tumour effects of CPT-11 were related to the CE concentration. Measuring the concentration of CE may allow the optimum dose of CPT-11 to be determined, opening up the possibility of individualized chemotherapy programmes.

Thermal electrocyclisation of the azahexatriene system has been used as a key step for the synthesis of anti-HIV and anti-tumour compounds, harman, derivatives of harman and 1-aryl-β-carbolines. A one-pot reaction sequence was used to furnish these compounds in good yield.

The title compound [CCDC 199359], C 1 6 H 2 0 N 5 crystallized in Monoclinic system with the space group C2/c. The unit cell parameters are: a = 16.554(6), b = 12.145(4), c = 16.221(5)A and β = 102.67(1)°. The molecular structure is stabilized by an intramolecular C-H...N type hydrogen bond and the molecular packing by the intermolecular C-H...N and N-H...N type hydrogen bonds.

An overview of the use of gold drugs in the alleviation of the symptoms associated with the debilitating disease rheumatoid arthritis (RA) is presented. Other potential therapies based on gold compounds, such as against parasitic diseases, HIV and asthma are summarised. The development of gold compounds as novel anti-tumour agents is also described. Compounds containing gold(I), as utilised in the treatment of RA, and gold(III), show exciting potential in this regard, there being some very potent compounds targeting biological targets, such as DNA, and displaying selectivity in their cytotoxic profiles. In conclusion, very real potential exists for the development of anti-tumour agents based on gold.