Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin, a newly described potent orexigenic peptide, may have therapeutic potential in patients with cachexia. We assessed whether pancreatic adenocarcinoma, commonly associated with marked cachexia, is a ghrelin-responsive malignancy. Pancreatic adenocarcinoma cells were exposed to ghrelin (0-100 nM). Proliferation was determined by MTT assay. Ghrelin, ghrelin 1a and 1b receptor expression and Akt phosphorylation were assessed. The effects of ghrelin (+/- its antagonist D-Lys-GHRP6, or the PI3-K inhibitor Wortmannin) on cellular motility and invasiveness were quantified by Matrigel Boyden chamber assay. All cell lines expressed ghrelin 1a and 1b receptor transcript and protein, but only PANC1 weakly expressed ghrelin transcript. Ten nanomolar ghrelin increased proliferation, motility, invasiveness, and Akt phosphorylation in all cell lines. Proliferation was affected dose-dependently, being suppressed at higher ghrelin concentrations. D-Lys-GHRP6 suppressed ghrelin-induced proliferation, invasion, and Akt phosphorylation. Wortmannin abolished the effects of ghrelin on motility and invasiveness. Pancreatic adenocarcinoma is a ghrelin-responsive malignancy.
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PMID:Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. 1295 Oct 72

Eight lichens were extracted successively with n-hexane, diethyl ether and methanol using a Soxhlet process. The cytotoxic activity of the 24 lichen extracts was evaluated in vitro using two murine (the L1210: lymphocytic leukaemia, and the 3LL: Lewis lung carcinoma) and four human (the K-562: chronic myelogenous leukaemia, the U251: glioblastoma, the DU145: prostate carcinoma, and the MCF7: breast adenocarcinoma) cancer cell lines and non-cancerous cells, the Vero cell line (African green monkey kidney cell line). The MTT assay revealed significant cytotoxicity (IC50 < or = 20 microg/ml) on one of the tested cancer cell lines for at least one extract of each lichen species. Some extracts of Cladonia convoluta, Cladonia rangiformis, Parmelia caperata, Platismatia glauca and Ramalina cuspidata demonstrated interesting activities particularly on human cancer cell lines as good selectivity indices were recorded (SI > 3).
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PMID:Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. 1367 34

Propranolol is a lipophilic nonselective beta blocker mainly eliminated via the liver. The specific architectural arrangement of the mammalian lung favors the filtration of so-called pneumophilic drugs out of the blood and retention within the tissue, as shown in particular for amphetamine, amiodarone, imipramine, chlorpromazine, propranolol and local anesthetics. In the current study we tested in vitro the susceptibility of freshly isolated rat type II pneumocytes (RTII), rat alveolar macrophages (RAM), human alveolar macrophages (HAM) and A549 human lung adenocarcinoma cell line (A549) to propranolol (0.001-1 mM). Cytotoxicity was evaluated by changes in membrane integrity (lactate dehydrogenase [LDH] assay) and mitochondrial metabolic activity (reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) after 3-h and 20-h incubation with propranolol. In all tested lung cells, propranolol caused concentration-dependent decreases of MTT reduction and LDH retention in the fraction of attached cells, which was associated with an increase of LDH activity in the medium and in the fraction of non-attached cells. After 3-h incubation, the reduction of MTT was significantly decreased compared with control at > or = 1 x 10(-4) M in HAM, at > or = 5 x 10(-4) M in A549 and significantly decreased of LDH retention in the fraction of attached cells in HAM and in A549 at > or = 5 x 10(-4) M. After 20-h incubation the reduction of MTT was significantly decreased compared with control at > or = 1 x 10(-6) M in RAM, at > or = 5 x 10(-5) M in RTII and HAM and > or = 5 x 10(-4) M in A549. Propranolol caused a significant decrease of LDH retention in the fraction of attached cells (> or = 5 x 10(-5) M, RAM and RTII; > or = 5 x 10(-4) M, HAM and A549). The cytotoxic effect of propranolol in HAM and A549 was more pronounced after prolongation of incubation time (from 3 h to 20 h). These results showed that rat and human lung cells were sensitive to propranolol concentration < or = 1 mM in vitro. We suppose that the damaging action of propranolol on the lungs might be mediated by physicochemical properties of moiety and its pulmonary metabolites.
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PMID:Propranolol cytotoxicity in rat and human lung in vitro. 1457 Dec 79

The main objective of this study is to exploit the solubilizing potential of hydroxypropylcellulose-g-polyoxyethylene alkyl ether (HPC-g-(POE)(y)-C(n)) polymeric micelles towards poorly water soluble drugs in order to improve their oral bioavailability. Hydrophobically modified HPC graft copolymers of various compositions were synthesized by attaching hexadecyl or octadecyl residues to the hydrophilic HPC backbone via short POE linkers of different lengths. The onset of micellization was estimated by fluorescence spectroscopy. The hydrodynamic diameter of different HPC-g-(POE)(y)-C(n) micelles was evaluated by dynamic light scattering (DLS). Cyclosporin A (CsA), a poorly water soluble immunosuppressant, was selected as model drug. CsA-loaded HPC-g-(POE)(y)-C(n) micelles were prepared by a dialysis procedure and the amount of CsA incorporated in the micelles was assayed by high-performance liquid chromatography. Following 24-h incubation with human colon adenocarcinoma, Caco-2 cells, the cytotoxicity of various HPC-g-(POE)(y)-C(n) copolymers was evaluated using the MTT colorimetric assay and compared to those of unmodified HPC and free (POE)(y)-C(n). In aqueous solution, different HPC-g-(POE)(y)-C(n) copolymers formed polymeric micelles of low critical association concentrations (CAC) and micelle mean diameters ranging from 78 to 90 nm. CsA loading into HPC-g-(POE)(y)-C(n) polymeric micelles was significantly larger than in unmodified HPC. It increased with increasing number of (POE)(y)-C(n) units grafted per HPC chain. On the cellular level, unmodified HPC showed no cytotoxicity, while free (POE)(y)-C(n) molecules inhibited cell growth. Most importantly, the study revealed that HPC-g-(POE)(y)-C(n) exhibited no significant cytotoxic effect.
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PMID:Solubilization of poorly water soluble drugs in micelles of hydrophobically modified hydroxypropylcellulose copolymers. 1460 22

Eighteen main compounds, including four norsesquiterpenoids (1-4) and 14 phenolic compounds (5-18) isolated previously from Phyllanthus emblica, together with a main constituent, proanthocyanidin polymers (19) identified at this time from the roots, were estimated for their antiproliferative activities against MK-1 (human gastric adenocarcinoma), HeLa (human uterine carcinoma), and B16F10 (murine melanoma) cells using an MTT method. All of the phenolic compounds including the major components 5-8 from the fruit juice, 8, 9, and 12 from the branches and leaves, and 19 from the roots showed stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Norsesquiterpenoid glycosides 3 and 4 from the roots exhibited significant antiproliferative activities, although their aglycon 1 and monoglucoside 2 showed no inhibitory activity against these tumor cells.
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PMID:Antiproliferative activity of the main constituents from Phyllanthus emblica. 1475 47

Recently, evidence has accumulated that weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) with leucovorin (LV, folinic acid) biochemical modulation may improve the response rates compared with the bolus 5-FU regimens in colorectal cancer (CRC). Combining the infusional 5-FU/LV (iFL) regimens with oxaliplatin or irinotecan is widely adopted to further improve treatment efficacy. Either oxaliplatin-iFL or irinotecan-iFL may achieve an overall response rate of more than 50% in the first-line treatment. Intriguingly, in the salvage treatment for metastatic CRC patients who had failed iFL, only oxaliplatin-iFL may achieve a response rate of about 13-25%. In contrast, oxaliplatin alone or irinotecan-iFL had a very low response rate of 5% or less. To test if the oxaliplatin may reverse the iFL-related 5-FU resistance in CRC, we used DLD-1 colon adenocarcinoma cells as the in vitro study model. First, we revealed that oxaliplatin and 5-FU act synergistically on DLD-1 cells by MTT cytotoxicity assay and median drug effect analysis. Second, we treated the DLD-1 cells with serial concentrations of oxaliplatin (0.1-10 microM). Oxaliplatin treatment results in down-regulation of free thymidylate synthase (TS) protein expression by Western blotting. Further, we analyzed the TS mRNA level by reverse transcription and real-time quantitative polymerase chain reaction assay. Oxaliplatin treatment results in down-regulation of the TS mRNA level up to 40% (mean +/- SD of ratio to reference control = 0.60 +/- 0.21, range 0.42-0.84). In this study, our data provide important information explaining the reason why the combination of oxaliplatin and 5-FU results in a better objective response in 5-FU-resistant patients than oxaliplatin alone does. Our data also suggest that TS down-regulation happens at the transcriptional level. TS modulation and down-regulation had, thus, shed light on the useful potential strategy to achieve objective responses in 5-FU-resistant CRC patients.
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PMID:Down-regulation of thymidylate synthase expression and its steady-state mRNA by oxaliplatin in colon cancer cells. 1505 42

The cytotoxic effect of isoflavonoids in the development of different forms of cancer has been reported by epidemiological and dietary studies. Consequently, there is a search for an accurate and reliable method for monitoring the interactions of these chemicals with cancerous cells. We have developed and optimized a fully autonomous electrochemical biosensor for studying the role of isoflavonoids on A549 lung adenocarcinoma cell line. This advanced biosensor uses a prototype 96-electrode (DOX-96) well-type device that allows the measurement of cell respiratory activity via the consumption of dissolved oxygen. The system provides a continuous, real-time monitoring of cell activity upon exposure to naturally occurring polyphenols, specifically resveratrol, genistein, and quercetin. The system is equipped with a multipotentiostat, a 96-electrode well for measurements and cell culturing with 3 disposable electrodes fitted into each well. A comparison with classical "cell culture" techniques indicates that the biosensor provides real-time measurement with no added reagents. A detection limit of 1 x 10(4) was recorded versus 200 and 6 x 10(3) cells/well for MTT and fluorescence assays, respectively. This method was optimized with respect to cell stability, reproducibility, applied potential, cell density per well, volume/composition of cell culture medium per well, and incubation. Others include total measuring time, temperature, and sterilization procedure. This study represents a basic research tool that may allow researchers to study the type, level, and specific influence of isoflavonoids on cells.
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PMID:Autonomous multielectrode system for monitoring the interactions of isoflavonoids with lung cancer cells. 1508 Jul 44

Ethanolic extracts of selected nine Thai medicinal plants were tested for antiproliferative activity against SKBR3 human breast adenocarcinoma cell line using MTT assay. Garcinia mangostana showed the most potent activity. However, all plant extracts showed activity in potential range for further investigation on cancer cells.
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PMID:Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line. 1515 99

In the present study, we detected the expression of SSTR3 protein in 40 patients with gastric adenocarcinoma and 40 cases of normal gastric mucosa by immunoperoxidased staining. SSTR3 mRNA and protein were also examined in gastric cancer cell lines and eternal gastric epithelial cell line by RT-PCR, immunofluorescence and Western blot. The effect of octreotide on the growth of gastric cancer cells was examined by MTT test, and the apoptosis by flow cytometry. Competitive protein binding method was also used to evaluate the role of SSTR3. The results were: (1) SSTR3 protein existed in the membrane of gastric cancer cells. In normal gastric mucosa, SSTR3 protein distributed to the cellular membrane and cytoplasm or interstitial tissue in submucosa. The expression of SSTR3 protein was significantly lower in gastric cancer compared with normal mucosa. Moreover, the poor-differentiated adenocarcinoma was lower than the well-differentiated adenocarcinoma, and the similar result in cell lines. (2) Octreotide could inhibit the growth and induce the apoptosis of gastric cancer and normal epithelial cells that expressed SSTR3, but didn't affect the cells with no or weakly expression of SSTR3. (3) When the cells were administrated octreotide in combination of SSTR3 antibody, the effect of octreotide decreased dramatically. The preliminary study suggested that SSTR3 might play a role in the growth and apoptosis of gastric cancer. In those gastric cancers that expressed SSTR3, octreotide could be effective in inhibiting cell growth and inducing cell apoptosis through mediation of SSTR3.
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PMID:The effect of somatostatin and SSTR3 on proliferation and apoptosis of gastric cancer cells. 1532 67

Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate wavelength of light, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Photofrin, a complex mixture of porphyrin oligomers has recently received FDA approval for the photodynamic treatment of esophageal and endobronchial carcinoma, but its photodynamic and toxicity profiles are far from ideal. In the present study we evaluated a series of porphyrin-based PSs, some of which newly synthesized by our group, with the aim to identify agents with more favorable characteristics. For the most effective compounds in the porphyrin series, chlorin analogs were also synthesized; for comparison, the screening also included Photofrin. Cytotoxicity studies were performed by the MTT assay on a cultured human colon adenocarcinoma cell line (HCT116); the results indicate that the 3,4,5-trimethoxyphenyl, 3OH- and 4OH-phenyl, and the sulfonamidophenyl derivatives are significantly more potent than Photofrin. Flow cytometric studies and fluorescence microscopy indicate that in PDT-treated HCT116 cells death occurs mainly by apoptosis. In summary, novel PSs described in the present study, belonging both to the porphyrin and chlorin series, have proven more effective than Photofrin in killing colon cancer cells in vitro; extending these observation to in vivo models, particularly regarding the deeper reaching chlorin derivatives, might lead to significant advances in the development of tumor PDT.
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PMID:Photodynamic effects of porphyrin and chlorin photosensitizers in human colon adenocarcinoma cells. 1533 64


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