Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paclitaxel is one of the best antineoplastic drugs found from nature in the past decades, which has been found effective against a wide spectrum of cancers including ovarian cancer, breast cancer, small and non small cell lung cancer, colon cancer, head and neck cancer, multiple myeloma, melanoma, and Kaposi's sarcoma. Like many other anticancer drugs, it has difficulties in clinical administration due to its poor solubility in water and most pharmaceutical reagents. In its current clinical application, an adjuvant called Cremophor EL has to be employed, which has been found to be responsible for many serious side effects. Nanoparticles of biodegradable polymers can provide an ideal solution to such an adjuvant problem and realize a controlled and targeted delivery of the drug with better efficacy and less side effects. With further development, such as particle size optimization and surface coating, nanoparticle formulation of paclitaxel can promote a new concept of chemotherapy to realize its full efficacy and to improve quality of life of the patients, which includes personalized chemotherapy, local chemotherapy, sustained chemotherapy, oral chemotherapy, chemotherapy across the blood-brain barrier, chemotherapy across the microcirculation barrier, etc. The present research proposes a novel formulation for fabrication of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) by a modified solvent extraction/evaporation technique, in which natural emulsifiers, such as phospholipids, cholesterol and vitamin E TPGS are creatively applied to achieve high drug encapsulation efficiency, desired drug released kinetics, high cell uptake and high cytotoxicity. The nanoparticles composed of various recipes and manufactured under various conditions were characterized by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) and Fourier Transformation Infrared Spectroscopy (FTIR) for surface chemistry, zeta-potential for surface charge, and differential scanning calorimetry (DSC) for the thermogram properties. The drug encapsulation efficiency and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was found that these natural emulsifiers have great advantages for nanoparticle formulation of paclitaxel over the traditional macromolecular emulsifiers, such as polyvinyl alcohol (PVA). Nanoparticles of desired small size and narrow size distribution can be obtained. The drug encapsulation efficiency can be achieved as high as 100 %. The released kinetics can be made under control. The HT-29 cancer cell line experiment showed that after 24 hours of incubation, the cell mortality caused by the drug administered by such nanoparticle formulation could be more than 13 times higher than that caused by the free drug under similar conditions.
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PMID:Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. 1496 22

The possible association between the risk of ovarian cancer and the levels of calcium and magnesium in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible ovarian cancer deaths (933 cases) of Taiwan residents from 1986 through 2000 were compared with a sample of deaths from other causes (933 controls), and the levels of calcium and magnesium in the drinking water of these residents were determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes, and the controls were pair-matched to the cases by sex, year-of-birth, and year-of-death. Compared to those with magnesium levels below 7.3 mg/liter, the adjusted odd ratios (95% confidence interval (CI)) were 0.71 (0.55-0.92) for the group with water magnesium levels between 7.3 and 13.4 mg/liter and 0.57 (0.43-0.76) for the group with magnesium levels of 13.5 mg/liter or more. The adjusted odd ratios were not statistically significant for the relationship between calcium levels in drinking water and ovarian cancer. The results of the present study show that there may be a significant protective effect of magnesium intake from drinking water on the risk of ovarian cancer death.
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PMID:Magnesium and calcium in drinking water and risk of death from ovarian cancer. 1508 66

A few epidemiologic studies have suggested that consumption of drinking water with high trihalomethane content increases the risk of cancer. We investigated the mortality of a cohort of 5144 residents in Guastalla, northern Italy, who were supplied tap water with high chloroform and trihalomethane content between 1965 and 1987. Using death rates of a nearby community as reference rates, the standardized mortality ratio from all cancers between 1987 and 1999 was slightly increased for both males (1.2, 95% confidence interval 1.1-1.4) and females (1.1, 95% confidence interval 1.0-1.3). This was mainly due to a higher mortality from stomach, liver, lung, prostate and bladder cancer in males and from stomach, pancreas, breast and ovarian cancer and lymphocytic leukemia in females. We also noted excess mortality from melanoma in both males and females. Overall, our findings were consistent with an association between trihalomethane exposure and increased cancer risk at some sites. However, the point estimates were statistically imprecise, due to the limited number of deaths for some site-specific cancers. In addition, we were unable to rule out the possibility of confounding due to smoking and other life-style factors with regard to some of the excess rates.
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PMID:A retrospective cohort study of trihalomethane exposure through drinking water and cancer mortality in northern Italy. 1532 57

Significant progress has been made in the management of advanced ovarian cancer. Response rates to platinum-based chemotherapy are respectable; however, recurrence continues to be the rule rather than the exception. Chemotherapy is administered as initial treatment and for disease recurrence, often over a period of many years--thus ovarian cancer is considered a chronic disease by many oncologists. The importance of the taxanes in the treatment of ovarian cancer is well established. However, taxanes are associated with numerous toxicities, resulting in the need for alternative dosing strategies that produce fewer side effects, or the discovery of novel taxanes with equivalent anti-tumor activity, but a more favorable toxicity profile. Several taxanes are in development including CT-2103, a macromolecule consisting of paclitaxel conjugated to a biodegradable, water-soluble polymer of glutamic acid. Clinical data of CT-2103 as a single agent and in combination have demonstrated activity in previously treated ovarian cancer patients, both in platinum-sensitive and platinum-resistant disease. CT-2103 appears to be potentially associated with a more favorable toxicity profile relative to paclitaxel, and enhanced solubility allows for a 10-minute infusion. Ongoing trials employing this agent will focus on extending survival, optimizing quality of life, and defining a possible role for CT-2103 in the standard management of advanced ovarian cancer.
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PMID:Improving the toxicity profile of chemotherapy for advanced ovarian cancer: a potential role for CT-2103. 1550 7

4-Anilinoquinazoline derivatives are widely investigated due to their potent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. Two 4-anilinoquinazolines with Lavendustin A subunit (10a,b) were synthesized and examined for their EGFR tyrosine kinase inhibitory activity as well as their antiproliferative properties on variant human cancer cell lines. Both compounds maintained their EGFR tyrosine kinase inhibitory activity at the 10-7 M level and led to significant growth inhibition in certain leukemia, non-small cell lung cancer (NSCLC), ovarian cancer, renal cancer and breast cancer cell lines with GI50 values at the 10-6 M level. There could not be observed any notable difference between 10a and 10b regarding to their antiproliferative activity. Interestingly, we observed the high tendency of 10a and 10b to include certain solvents, e.g. water, DMF, DMSO, which may be due to the remarkable number of hydrogen accepting/donating groups in 10a and b. An X-ray analysis of 10a including water and DMF illustrates a possible hydrogen bond pattern and could serve as information for preferred receptor (e.g. EGFR tyrosine kinase) binding sites. Finally, we aimed for irreversible EGFR tyrosine kinase inhibitors. The p-quinone derivatives 11a and 11b, which contain a Michael acceptor position according to the irreversible inhibitor CI-1033, could be derived from the p-hydroquinone derivatives 10a or 10b, respectively, by oxidation. However, due to their instability 11a and 11b could not be obtained in a pure form.
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PMID:4-Anilinoquinazolines with Lavendustin A subunit as inhibitors of epidermal growth factor receptor tyrosine kinase: syntheses, chemical and pharmacological properties. 1557 62

Our study focused on aromatase cytochrome P450 (CYP19) expression in ovarian epithelial normal and cancer cells and tissues. Aromatase mRNA expression was analyzed by real-time PCR in ovarian epithelial cancer cell lines, in human ovarian surface epithelial (HOSE) cell primary cultures, and in ovarian tissue specimens (n=94), including normal ovaries, ovarian cysts and cancers. Aromatase mRNA was found to be expressed in HOSE cells, in BG1, PEO4 and PEO14, but not in SKOV3 and NIH:OVCAR-3 ovarian cancer cell lines. Correlation analysis of aromatase expression was performed according to clinical, histological and biological parameters. Aromatase expression in ovarian tissue specimens was higher in normal ovaries and cysts than in cancers (P<0.0001). Using laser capture microdissection in normal postmenopausal ovaries, aromatase was found to be predominantly expressed in epithelial cells as compared to stromal component. Using immunohistochemistry (IHC), aromatase was also detected in the epithelium component. There was an inverse correlation between aromatase and ERalpha expression in ovarian tissues (P<0.001, r=-0.34). In the cancer group, no significant differences in aromatase expression were observed according to tumor histotype, grade, stage and survival. Aromatase activity was evaluated in ovarian epithelial cancer (OEC) cell lines by the tritiated water assay and the effects of third-generation aromatase inhibitors (AIs) on aromatase activity and growth were studied. Letrozole and exemestane were able to completely inhibit aromatase activity in BG1 and PEO14 cell lines. Interestingly, both AI showed an antiproliferative effect on the estrogen responsive BG1 cell line co-expressing aromatase and ERalpha. Aromatase expression was found in ovarian epithelial normal tissues and in some ovarian epithelial cancer cells and tissues. This finding raises the possibility that some tumors may respond to estrogen and provides a basis for ascertaining an antimitogenic effect of AI in a subgroup of ovarian epithelial cancers.
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PMID:Aromatase expression in ovarian epithelial cancers. 1574 28

Topotecan (Hycamtin) is a water soluble semisynthetic analogue of the alkaloid camptothecin which has antitumour activity in preclinical models in vitro and in vivo. A range of Phase I studies has been performed and a daily x 5 iv. schedule, which showed most promising evidence of activity, was selected for extensive clinical evaluation. To date, topotecan has been shown to be active in a number of malignancies, including metastatic ovarian cancer, recurrent small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), breast cancer, colorectal cancer and myelodysplastic syndrome. In ovarian cancer, response rates of around 15% were identified in patients who had failed standard chemotherapy, and in a randomised, comparative study with paclitaxel response rates of 20% (topotecan) and 13% (paclitaxel) were observed. In addition, overall time to progression was impressive at 23 weeks (topotecan) compared with 14 weeks (paclitaxel). In recurrent SCLC, topotecan has shown good activity in sensitive patients with a response rate of 39%, although the response rate in refractory patients was considerably lower (7%). Median survival of all patients was 5.4 months, acceptable for this difficult clinical scenario. Topotecan is well-tolerated in the majority of patients and subjective toxicities are uncommon. The principal side-effect is myelosuppression, mainly neutropenia. Serious clinical sequelae are relatively uncommon and non-cumulative. Nonhaematological toxicities are generally mild and not dose-limiting. In clinical use, topotecan has exhibited activity in multiple tumour types, with a side-effect profile that is predictable and manageable. The drug is under evaluation in other tumour types and in combination chemotherapy regimens.
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PMID:Topotecan, an active new antineoplastic agent: review and current status. 1598 23

Organometallic compounds offer broad scope for the design of therapeutic agents, but this avenue has yet to be widely explored. A key concept in the design of anticancer complexes is optimization of chemical reactivity to allow facile attack on the target site (e.g., DNA) yet avoid attack on other sites associated with unwanted side effects. Here, we consider how this result can be achieved for monofunctional "piano-stool" ruthenium(II) arene complexes of the type [(eta6-arene)Ru(ethylenediamine)(X)]n+. A potentially important activation mechanism for reactions with biomolecules is hydrolysis. Density functional calculations suggested that aquation (substitution of X by H2O) occurs by means of a concerted ligand interchange mechanism. We studied the kinetics and equilibria for hydrolysis of 21 complexes, containing, as X, halides and pseudohalides, pyridine (py) derivatives, and a thiolate, together with benzene (bz) or a substituted bz as arene, using UV-visible spectroscopy, HPLC, and electrospray MS. The x-ray structures of six complexes are reported. In general, complexes that hydrolyze either rapidly {e.g., X = halide [arene = hexamethylbenzene (hmb)]} or moderately slowly [e.g., X = azide, dichloropyridine (arene = hmb)] are active toward A2780 human ovarian cancer cells, whereas complexes that do not aquate (e.g., X = py) are inactive. An intriguing exception is the X = thiophenolate complex, which undergoes little hydrolysis and appears to be activated by a different mechanism. The ability to tune the chemical reactivity of this class of organometallic ruthenium arene compounds should be useful in optimizing their design as anticancer agents.
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PMID:Controlling ligand substitution reactions of organometallic complexes: tuning cancer cell cytotoxicity. 1635 26

PABA/NO is a diazeniumdiolate of structure Me(2)NN(O)=NOAr (where Ar is a 5-substituted-2,4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic acid). It has shown activity against human ovarian cancer xenografts in mice rivaling that of cisplatin, but it is poorly soluble and relatively unstable in water. Here we report structure-based optimization efforts resulting in three analogues with improved solubility and stability in aqueous solution. We sought to explain PABA/NO's physicochemical uniqueness among these four compounds, whose aminobenzoic acid precursors differ structurally only in the presence or absence of the N-methyl group and/or the position of the carboxyl moiety (meta or para). Studies revealed that PABA/NO's N-methyl-p-aminobenzoic acid substituent is bound to the dinitrobenzene ring via its carboxyl oxygen while the other three are linked through the aniline nitrogen. This constitutes a revision of the previously published PABA/NO structure. All four analogues reacted with GSH to produce bioactive nitric oxide (NO), but PABA/NO was the most reactive. Consistent with PABA/NO's potent suppression of A2780 human ovarian cancer xenograft growth in mice, it was the most potent of the four in the OVCAR-3 cell line.
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PMID:PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution chemistry, reactivity toward glutathione, and in vitro activity. 1645 Oct 80

Cisplatin is a potent anticancer drug with low solubility in water. A new type of highly stable polymer micelles, namely core-surface-crosslinked nanoparticles (SCNPs) made from amphiphilic brush copolymers, were evaluated as the carrier of cisplatin. Cisplatin could be loaded in the SCNPs with poly(epsilon-caprolactone) (PCL) cores and hydrophilic poly(ethylene glycol) (PEG) or poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMA) shells with high loading efficiency (approximately 90%). In vitro cellular uptake experiments indicated that both SCNPs could be easily taken up by SKOV-3 ovarian cancer cells. Both cell proliferation assay and IC50 measurements indicated that cisplatin encapsulated in the SCNPs had much enhanced cytotoxicity to the cancer cells compared to free cisplatin. The positive charges on the PCL/PDMA SCNPs promoted the cellular internalization of the nanoparticles, resulting in higher cytotoxicity of cisplatin in these SCNPs. The IC50 of the cisplatin encapsulated in PCL/PDMA SCNPs was as low as 0.01 microg/mL, lower than that of cisplatin in PCL/PEG SCNPs and free cisplatin.
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PMID:Highly stable core-surface-crosslinked nanoparticles as cisplatin carriers for cancer chemotherapy. 1649 89


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