Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils were intra-cellularly "loaded" with the chemotherapeutic agent, doxorubicin applying a variety of incubation conditions in order to identify parameters which maximize chemotherapeutic incorporation, while simultaneously preserving optimal viability and chemotactic responsiveness. Doxorubicin "loaded" neutrophils (DLN) were produced in triplicate at different combinations of incubation conditions such as temperature (4 degrees C, 37 degrees C); duration (0, 1, 2 hours); and doxorubicin concentration (20, 40, 60 micrograms/ml). Chemotactic responsiveness of rinsed DLN preparations was subsequently assessed against the neutrophil peptide chemotactic agent, formyl methionyl leucyl phenylalanine (fMLP, 10(-6) M) utilizing a modified 96-well Boyden chemotactic chamber apparatus. Viable, fMLP-responsive DLN preparations were subsequently detected with MTT vitality staining reagent. At sub-physiological incubation temperatures (4 degrees C), profound declines in the viability of DLN preparations were detected when simultaneously incubated with doxorubicin formulated at concentrations greater than 10 micrograms/ml. In contrast, DLN preparations incubated at 37 degrees C displayed diminished viability only when incubated with doxorubicin formulated at a concentration of 60 micrograms/ml. Viable DLN populations were subsequently evaluated to determine their ability to exert in vitro cytotoxic activity against monolayer populations of human mammary carcinoma (HTB-19) propagated in a tissue culture environment. The lethal effect which DLN preparations inflicted towards HTB-19 populations was substantially greater than was observed with an equivalent population of untreated neutrophils. Maximal in vitro cytotoxic activity was detected with DLN preparations produced at 37 degrees C in the presence of doxorubicin formulated at a concentration of 40 micrograms/ml. In contrast, DLN preparations produced at an incubation temperature of 37 degrees C, and a doxorubicin concentration of 20 micrograms/ml displayed relatively lower levels of in vitro cytotoxic activity against HTB-19 monolayer populations. The degree of in vitro cytotoxic activity exerted against HTB-19 monolayer populations by DLN preparations was directly influenced by the duration of the challenge period. Maximal in vitro cytotoxic activity was observed when HTB-19 monolayer populations were challenged with DLN preparations for a period of 96-hours duration at 37 degrees C. Challenge periods of 48-hours duration produced levels of in vitro cytotoxic activity which were substantially lower than those observed for challenge periods of 96-hours duration. Optimal in vitro cytotoxic activity was recognized when DLN preparations were allowed to establish direct contact with HTB-19 monolayer populations at an estimated DLN:HTB-19 cellular ratio of approximately 5:1 (37 degrees C, CO2, 6%). Significantly less in vitro cytotoxic activity was recognized when DLN preparations were only permitted indirect cellular contact with HTB-19 monolayer populations which was achieved through the application of a semi-permeable 3 microM pore membrane partition. In vitro cytotoxic activity of DLN populations was not inhibited by the anti-oxidant agent, dimethyl sulfoxide (DMSO), but was inhibited in the presence of glutathione (GSH), superoxide dismutase (SOD), and vitamin E (alpha-tocopherol). Similarly, in vitro cytotoxic activity of DLN populations was also inhibited in the presence of sodium heparin (serine esterase inhibitor), and dexamethasone (inhibitor of neutrophil activation-degranulation phenomenon). Experimental results observed in these investigations collectively imply that the in vitro cytotoxic activity exerted by DLN preparations against HTB-19 populations is in part attributable to neutrophil-mediated cytotoxic immunity. This innate property of neutrophil populations involves their capacity to generate highly reactive oxygen "free" radical species (O2, HO, H2O2), and synthes
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PMID:Cytotoxic activity of doxorubicin "loaded" neutrophils against human mammary carcinoma (HTB-19). 937 37

When epithelial cells reach confluency in vitro, a number of energy-requiring activities such as growth and motility are contact-inhibited. We investigated the possible role of the E-cadherin/catenin complex, which acts as an invasion suppressor, in contact inhibition. Three strategies for modulation of the complex were used. Firstly, the cell-cell adhesion and signal transduction functions of E-cadherin were neutralized immunologically in human MCF-7/6 mammary carcinoma cells possessing a complete complex. Secondly, the effect of E-cadherin transfection in E-cadherin negative cell lines was investigated. Thirdly, alpha-catenin deficient variants of the human HCT-8/S11 colon carcinoma cell line were compared with their parent cells. In confluent cultures functional downregulation of the E-cadherin/catenin complex did not alter cell growth nor saturation density. This was shown by cell number counts, protein staining assays, cell cycle analysis, proliferation markers (Ki67 and Proliferating Cell Nuclear Antigen) and apoptosis assays. However, confluent cells with a functionally deficient complex showed positional instability and enhanced succinate dehydrogenase-mediated mitochondrial 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl) tetrazolium bromide (MTT) conversion, as compared to cells with an active complex. Our data indicate that contact inhibition of motility and of mitochondrial enzyme activity, but not of growth is regulated by the E-cadherin/catenin complex in epithelial cells.
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PMID:Functional downregulation of the E-cadherin/catenin complex leads to loss of contact inhibition of motility and of mitochondrial activity, but not of growth in confluent epithelial cell cultures. 943 30

It has been recognized that alpha-fetoprotein (AFP), as an oncofetal antigen, is re-expressed in large amounts in adult tumor cells and serves clinically useful purposes in tumor-marker assays. However, its biological activities are still undefined. In the present study, the ability of AFP to stimulate tumor-cell growth was observed by an in vitro experimental system. Mouse ascites cancer cells derived from hepatoma-22(H-22) or Ehrlich ascites carcinoma(EAC) were extracted intraperitoneally and cultured in RPMI 1640 medium containing 10% newborn calf serum for 48 hr. Cell growth was quantitated by a colorimetric assay using a MTT microculture tetrazolium dye. The results demonstrated that AFP significantly increased H-22-cell proliferation, with stimulation per cents of 122 to 156%. A similar growth-promoting effect of AFP was observed using EAC cells, with stimulation per cents of 86 to 210%. Moreover, the growth-stimulatory activity of AFP could be abrogated with anti-AFP antibodies. In addition, 5-fluorouracil could obviously inhibit AFP-induced proliferation of H-22 or EAC cells in vitro. These results suggest that AFP is associated with tumor-cell growth and may serve as an important target of tumor therapy.
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PMID:Stimulation of tumor-cell growth by alpha-fetoprotein. 946 62

A new experimental therapy for squamous carcinoma was tested by sensitizing human tumor cells with light-sensitive anticancer drugs followed by laser illumination at visible or infrared wavelengths. The anthrapyrazole DUP-941 and the isoquinoline derivative DUP-840 were compared with the dianthraquinone hypericin. P3 human squamous carcinoma cells were incubated for 2 h with the drugs at escalating doses ranging from 5 to 100 micrograms/ml, then exposed to visible green 532-nm or infrared 1064-nm light at 300 J output from a KTP/Nd:YAG laser. Tumor cell toxicity measured by in vitro MTT viability assays was minimal after DUP-840 uptake but was slightly enhanced by infrared laser emissions. By contrast, the strong tumoricidal effects seen after DUP-941 uptake were amplified over 10-fold by 532-nm light and up to 2-fold by 1064-nm light. Hypericin-sensitized tumor cells were killed after 532 nm irradiation even at the lowest drug dose but were not affected by 1064-nm illumination. The results suggest that laser chemotherapy with drugs sensitive to photothermal energy could become a useful new treatment modality for cancer.
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PMID:Laser chemotherapy of human carcinoma cells with three new anticancer drugs. 946 37

A 71-year-old woman underwent radical resection in May 1994 for a mediastinal mass invading the anterior chest wall. Histopathological examination revealed adenosquamous cell carcinoma. She was treated with postoperative chemotherapy including 5-fluorouracil (5-FU) and 4'-D-tetrahydropyrayl-doxorubicin (THP), based on in vitro chemosensitivity testing (CST), by MTT assay, using a surgical specimen. In December 1994, a recurrent tumor was detected on the left anterior chest wall and the patient received two courses of 5-FU, THP and methotrexate (MTX). The size of the chest-wall tumor decreased 25%. In July 1995, the patient had involvement of the left axillary lymph node and brain metastases in addition to the mass on the chest wall. Therefore, cisplatin, 5-FU and MTX were selected as treatment agents, based on CST using a metastatic axillary lymph node. After two courses of these agents, chest computed tomography showed a 91% reduction in the size of the chest wall tumor. Radiation was administered for the brain metastasis. In March 1997, the patient died of thymic carcinoma.
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PMID:[Successful chemotherapy based on in vitro chemosensitivity testing in a case of recurrent thymic carcinoma]. 952 32

The antitumor antibiotic doxorubicin was conjugated with polymeric dextrans of various molecular weights and the cytotoxicity of the conjugates against human carcinoma KB-3-1 cells and its multidrug-resistant subclone KB-V-1 cells was measured by tetrazolium salt MTT assay. The conjugates were much less toxic to the KB-3-1 cells than the free doxorubicin but exhibited similar toxicity to the KB-V-1 cells. The conjugate-DNA interactions were monitored in real-time using an optical biosensor based on evanescent wave detection to obtain the association (ka) and dissociation (kd) rate constants as well as the equilibrium binding constants (KA) of the bindings. Both ka and kd values for the conjugates are more than three magnitudes smaller than those for free doxorubicin, while the KA values of the conjugate-DNA complexes are only about 10 times smaller than that of the free doxorubicin-DNA complex. The results indicate that the cytotoxicity and the DNA-binding kinetics of doxorubicin may be modified with dextran conjugation. The KA values obtained from the biosensor measurements were in close agreement with those determined in solution by fluorescent titration method, verifying the utility of the label-free biosensing measurements as an efficient method for studying ligand-DNA interactions.
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PMID:Cytotoxicity and DNA binding characteristics of dextran-conjugated doxorubicins. 955 82

d-Dicentrine, a naturally occurring aporphine type isoquinoline alkaloid, isolated from the root of Lindera megaphylla Hemsl. (Lauraceae), was evaluated for its potential anti-cancer activity. We found d-dicentrine significantly inhibited the growth of human hepatoma cell line HuH-7 by delaying its doubling time in tissue culture. An in vitro colony forming assay showed that d-dicentrine decreased the colony formation efficiency in both hepatoma cell lines, HuH-7 and MS-G2, used in our study. Biosyntheses of the macromolecules DNA and RNA were also strongly inhibited. An MTT assay in 21 tumor cell lines also revealed that d-dicentrine was most cytotoxic to esophageal carcinoma HCE-6, lymphoma cell lines Molt-4 and CESS, leukemia cell lines HL60 and K562, and hepatoma cell line MS-G2. An in vitro tumor growing assay in the Severe Combined immunodeficiency (SCID) mice showed that intraperitoneal injection of d-dicentrine at the dose of 100 micrograms twice a week for 4 weeks significantly inhibited the tumor incidence of leukemia cell line K562 in SCID mice. All these data indicated that d-dicentrine has potential anti-tumor applications.
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PMID:Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla. 958 16

The chemosensitivities of 27 fresh specimens of head and neck cancers were tested with MTT assay to study the practicability and accuracy of the assay for the examination of chemosensitivity in head and neck cancer patients. The chemosensitivities among cancers of different primary sites, pathologic types, histological differentiations, DNA ploidies and estrogen receptors were compared in an attempt to evaluate the choice of anticancer drugs for individual chemotherapy. Eight anticancer drugs: Methotroxate (MTX), Mitomycin C (MMC), fluorouracil (5-Fu), Carboplatin (CBDCA), Pingyangmycin (PYM), Homoharringtonine (HHA), Etoposid (VP16) and Vincristine (VCR) were included. The success rate of MTT assay in the present study was 92.6% and the accuracy was relatively high. The sensitivity sequence was PYM > HHA > MTX > CBDCA > MMC > 5-Fu > VCR > VP16, which suggested HHA should be recommended first to the chemotherapy of head and neck cancer. No chemosensitivity differences were found among different primary sites histological differentiations and estrogen receptors. The chemosensitivity of squamous cell carcinoma was significantly higher than that of adenoid cystic carcinoma. The chemosensitivity of aneuploid tumor was significantly higher than that of diploid.
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PMID:[Chemosensitivity test for head and neck cancers]. 964 44

The molecular mechanism(s) by which tumor cells survive after exposure to ionizing radiation are not fully understood. Exposure of A431 cells to low doses of radiation (1 Gy) caused prolonged activations of the mitogen activated protein (MAP) kinase and stress activated protein (SAP) kinase pathways, and induced p21(Cip-1/WAF1) via a MAP kinase dependent mechanism. In contrast, higher doses of radiation (6 Gy) caused a much weaker activation of the MAP kinase cascade, but a similar degree of SAP kinase cascade activation. In the presence of MAP kinase blockade by the specific MEK1 inhibitor (PD98059) the basal activity of the SAP kinase pathway was enhanced twofold, and the ability of a 1 Gy radiation exposure to activate the SAP kinase pathway was increased approximately sixfold 60 min after irradiation. In the presence of MAP kinase blockade by PD98059 the ability of a single 1 Gy exposure to cause double stranded DNA breaks (TUNEL assay) was enhanced at least threefold over the following 24-48 h. The increase in DNA damage within 48 h was also mirrored by a similar decrease in A431 cell growth as judged by MTT assays over the next 4-8 days following radiation exposure. This report demonstrates that the MAP kinase cascade is a key cytoprotective pathway in A431 human squamous carcinoma cells which is activated in response to clinically used doses of ionizing radiation. Inhibition of this pathway potentiates the ability of low dose radiation exposure to induce cell death in vitro.
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PMID:Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell killing by low dose ionizing radiation in A431 human squamous carcinoma cells. 965 46

To evaluate the effects of dietary fats on breast cancer growth and metastasis, KPL-1 human breast carcinoma cells which have a propensity for axillary lymph node metastasis when inoculated into the thoracic mammary fat pad of female nude mice were examined. The mice were fed one of three semipurified diets containing 9.5% eicosapentaenoic acid plus 0.5% linoleic acid (EPA diet), 10% linoleic acid (LA diet), or 9.5% palmitic acid plus 0.5% linoleic acid (PA diet), or commercial laboratory chow containing 8.5% fat of which 4.1% was LA, 1.1% was PA, 0.06% was EPA, and 3.24% was other (Standard diet) starting 19 days before tumor cell inoculation and continuing until the end of the experiment (43 days after tumor cell inoculation). The tumor growth was faster and at a higher incidence in the mice fed the LA diet, and much slower and at a lower incidence in the EPA diet group compared with the mice fed the PA or Standard diet; the two separate experiment demonstrated identical results. The differences in tumor weight between the LA and PA groups and between the PA and EPA groups were significant (P < 0.05, respectively) at the termination of the experiment; the differences were due to different tumor cell proliferation rates. In an in vitro MTT assay, fatty acids showed direct stimulatory or inhibitory effects on the KPL-1 cells. Lymph node metastasis was seen in the LA and Standard diet groups, whereas it was not seen in the PA or EPA groups. The body weights were significantly lighter in the LA and EPA groups compared with the PA and Standard diet groups (P < 0.05, respectively). The results indicate that the EPA diet produced a reduction in tumor cell growth and metastasis whereas the LA diet had an enhancing effect on these parameters; dietary fatty acids may thus have a direct role in the growth and metastasis of human breast carcinoma independent of their systemic effects.
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PMID:Dietary effects of fatty acids on growth and metastasis of KPL-1 human breast cancer cells in vivo and in vitro. 967 80


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