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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the impressive antitumor activity of cisplatin, two major limitations of the drug, that is severe side effects and drug-resistance of cancer cells, make its use difficult for cancer therapy. These limitations have resulted in a great deal of effort having been expended into structural modifications of cisplatin. In this study, we tested two novel cisplatin analogues, (CPA)2Pt [DOLYM] (COMP-I) and (DACH)Pt[DOLYM] (COMP-II), for the mode of cytotoxic action against human tumor cells comparing with cisplatin and carboplatin in vitro. These two novel analogues had considerable cytotoxic activities against five kinds of human solid tumor cells, and especially COMP-II was more effective on HCT15 colon cancer cells than other compounds. In addition, COMP-II had cytostatic activity at low concentrations (10-0.3 microgram/ml), but other compounds revealed little effect on tumor growth at the low concentration.
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PMID:Cytotoxicity of two novel cisplatin analogues, (CPA)2Pt[DOLYM] and (DACH)Pt[DOLYM], to human cancer cells in vitro. 1023 May 5

Solid tumors commonly contain regions with glucose-starved and hypoxic conditions. Tumor cells under the adverse conditions can survive through the stress response, such as cell cycle arrest. In this study, we found that the stress conditions stimulated nuclear accumulation of proteasomes, large multicatalytic protease complexes, in human colon cancer HT-29 cells. The nuclear proteasome levels both in amount and in activity were increased approximately 4 and 2 times by glucose starvation and hypoxia, respectively. No changes were detected in the total expression levels of proteasome. The nuclear proteasome accumulation was also observed in ovarian cancer A2780 cells under glucose starvation, suggesting that this response was regardless of the origin of cancer cells. Our results indicate that the nuclear proteasome distribution is enhanced by glucose starvation and hypoxia, and suggest that the proteolysis by proteasome in the nucleus may play roles in the stress response of solid tumor cells.
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PMID:Glucose starvation and hypoxia induce nuclear accumulation of proteasome in cancer cells. 1032 7

Invasive growth of malignant cells, particularly carcinoma cells, induces host reaction within and around tumor tissue. Representatives of them are desmoplasia, angiogenesis and immune reactions. Desmoplasia, a process of fibrosis, is induced by activation of fibroblasts with increased production of matrix proteins and matrix degrading enzymes. Angiogenesis is prerequisite for the growth of solid tumor. Inhibition of this is now a target of cancer therapy. The present author has proposed a concept that tumor vessels are composed of nutrient vessels and immune/inflammatory vessels. The latter is similar to venules in inflammatory lesions expressing the cell adhesion molecules to facilitate the transmigration of inflammatory cells to the tissue. In colon cancer, venules distributed along the invasive margin correspond to these vessels, which express E-, and P-selectins, and ICAM-1. These venules are considered to be an entry site of immune/inflammatory cells to cancer tissue. To further analyze immune mechanism, the present authors have confirmed that macrophages distributed along the invasive margin of colon cancer express costimulatory molecules B7.1/B7.2, which are required for the proliferation of T-cells. T-cells were co-localized with these cells. Clinicopathologic analysis confirmed that CD8+ T-cells distributed within cancer cell nest (intraepithelial) have the most significant impact on the patients' survival in colorectal cancer. These data suggest that various host reactions take place in the stroma of cancer tissue, which modulate the biologic behavior of cancer.
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PMID:Pathophysiologic significance of host reactions in human cancer tissue: desmoplasia and tumor immunity. 1045 76

DNA diagnosis is useful and significant for clinical oncology, but its use is limited due to a difficulty in preparing tumor-derived DNA materials. To overcome this problem, we investigated the characterization of plasma DNA and it application to successfully detecting K-ras mutation at codon 12 in normal persons, hematopoietic neoplasms, and solid tumors. The range of plasma DNA in each group was 15.8 +/- 5.2 ng/ml, 43.3 +/- 29.8 ng/ml, and 26.8 +/- 17.0 ng/ml, respectively. The ranges in patients with solid tumor were gradually decreased to the normal level of around 15 ng/ml in 3 weeks postoperatively. Plasma DNAs consisted of about 200 bp DNA fragmentation and were convenient for PCR amplification of K-ras gene. The mutation at codon 12 by PCR-RFLP analysis was detected in 13(27%) of 49 patients with solid tumors such as pancreatic cancer, breast cancer, colon cancer, and gastric cancer. The diagnostic specificity was 100%. Serial observations by the PCR-RFLP analysis revealed disappearance of the mutant K-ras about 7 days after successful curative surgery in a patient with gastric cancer.
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PMID:[Characteristics of plasma DNA and its application for detection of K-ras gene mutation]. 1089 74

New drug development requires simple in vitro models that resemble the in vivo situation more in order to select active drugs against solid tumours and to decrease the use of experimental animals. In this paper, we review the characteristics and scope of a relatively simple cell-culture system with a three-dimensional organisation pattern - the multilayered postconfluent cell culture model. Solid tumour cell lines from diverse origins when grown in V-bottomed microtiter plates reach confluence in 3-5 days and then start to form multilayers. The initial exponential growth of the culture is followed by a plateau phase when cells reach confluence. This produces changes in the morphology of the cells. For some cell lines, it is possible to observe cell differentiation. A substantial advantage of the system is the use of the sulforodamine B (SRB) assay to determine relative cell growth or viability, which allows semiautomation of the experiments. Several experiments were performed to assess the differences and similarities between cells cultured as monolayers and multilayers, and eventually, compared with the results for solid tumours and some other models such as spheroids. Cell-cycle analysis for multilayers showed a lower S-phase arrest, which is accompanied by a decrease in the expression of cell-cycle-related proteins and a decrease in cellular nucleotide pools. Gene and protein expression of topoisomerase I, topoisomerase II and thymidylate synthase expression were lower for multilayers, but no substantial changes were observed for the expression of DT-diaphorase. P53 expression increased. Multilayer cultures present distinctive properties for drug transport across the membrane, drug accumulation and retention. In fact, the transport of antifolates across the membrane, accumulation of topotecan and gemcitabine-triphosphate are reduced in multilayers when compared with monolayers, which may be related to a decrease in drug penetration to the inner regions of the multilayers. Alteration of these pharmacodynamic parameters is directly related to a decrease in drug activity. The most powerful application of multilayers is in the assessment of cytotoxicity. Solid tumour cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The data show that multilayers are more resistant to the drugs than the corresponding monolayers, but there are substantial differences between the drugs depending on culture conditions, e.g. the difference was rather small for a drug such as cisplatin, miltefosine and EO9, a drug, which is activated under hypoxic conditions. Gemcitabine was active against ovarian cancer but not against colon cancer, resembling the in vivo situation. This observation was not evident with monolayer experiments. Another interesting application is the possibility to perform drug combination studies. The combination of gemcitabine and cisplatin proved to produce selective cell kill in H322 cells (non-small cell lung cancer cell line). Neither of the drugs was independently able to produce similar effects. In summary, multilayer cultures are relatively simple three-dimensional systems to study the effect of microenvironmental conditions on anticancer drug activity. The model might serve as a base for a more rigorous secondary in vitro screening.
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PMID:The multilayered postconfluent cell culture as a model for drug screening. 1103 3

Our understanding of the biology of colon cancer has matured to the point that it is a useful general paradigm for understanding solid tumor development. Recent advances provide insight into the genetic alterations underlying the development of colon cancer. These insights provide unique opportunities for genetic testing in predisposed, asymptomatic patients that can direct screening efforts and their clinical management. This review examines several inherited colon cancer predispositions, well described clinically for a century, that are now amenable to genetic testing. Additional discussion focuses on colon cancer predisposition traits that occur with high frequency but low penetrance characteristics. Finally, genetic tests for tumor markers that potentially have prognostic or therapeutic implications are reviewed.
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PMID:Genetic syndromes and genetic tests in colorectal cancer. 1105 48

From the supernatant of rabbit bone marrow, we isolated an organ-specific factor, which was related with the metastasis of prostate cancer to the bone and examined its adhesion to prostate cancer cells (PC-3). Molecular weight and amino acid sequence analyses of the active component obtained by high performance liquid chromatography revealed that a component identical to the alpha chain of hemoglobin accounted for 80% of the biological activity. Hemoglobin showed over 50% adhesion to PC-3 cells but only 10% adhesion to human colon cancer cell lines, representative of organ non-specific metastasis, and leukemia cells line, representative of a non-solid tumor. Some substance in the bone marrow may promote the first step of adhesion of cancer cells to bone marrow in the metastasis of prostate cancer to the bone, possibly an amino acid sequence or some tertiary structure similar to hemoglobin.
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PMID:Human prostate cancer cells adhere specifically to hemoglobin: a possible role in bone-specific metastasis. 1152 Jun 4

Aromatic fatty acids such as phenylbutyrate (PB) and its metabolite phenylacetate (PA) induce growth arrest, differentiation and apoptosis in solid tumor cells. Despite their antiproliferative action they were reported to exhibit a synergistic effect in combination with cytotoxic drugs like topotecan, and others. Since the activity of the camptothecines (CPTs) depends on local pH conditions, we investigated, whether PB/PA modulate CPT effects indirectly by affecting intracellular pH in SW620 and SW480 colon cancer cells. The results for the colon carcinoma cells show an antagonistic interaction for the combination of CPT and 0.25-5 mM PA in viability assays, resulting in an approximately 3-fold increase in IC50 (control: 20+/-7 nM). A synergistic effect with significantly increased numbers of late apoptotic/necrotic cancer cells (difference +21+/-4%) and 1.4-fold sensitization were detected upon inclusion of 2.5 mM PA during a 4-h CPT (10 micro;M) loading phase. In response to 0.25-1 mM PA/PB the cells exhibit a reversible decrease of pHi (0.1-0.31 pH units) in HEPES- or bicarbonate-buffered media. Dose-dependent acidification and pHi-recovery occurred following addition of PA and PB after an acid load and inhibition of the Na+/H+-antiporter and bicarbonate exchangers, pointing to a possible intracellular mechanism of cytoplasmic acidification. It is concluded that the synergistic modulation of CPT toxicity by short-term PA/PB treatment in colon carcinoma cells is caused by changes in intracellular pH, possibly affecting quantity and localization of the active closed lactone form of this drug.
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PMID:The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification. 1160 11

To help define the safety profile of the use of adenovirus (Ad) gene transfer vectors in humans, this report summarizes our experience since April 1993 of the local administration of E1(-)/E3(-) Ad vectors to humans using low (<10(9) particle units) or intermediate (10(9)-10(11) particle units) doses. Included in the study are 90 individuals and 12 controls, with diverse comorbid conditions, including cystic fibrosis, colon cancer metastatic to liver, severe coronary artery disease, and peripheral vascular disease, as well as normals. These individuals received 140 different administrations of vector, with up to seven administrations to a single individual. The vectors used include three different transgenes (human cystic fibrosis transmembrane conductance regulator cDNA, E. coli cytosine deaminase gene, and the human vascular endothelial growth factor 121 cDNA) administered by six different routes (nasal epithelium, bronchial epithelium, percutaneous to solid tumor, intradermal, epicardial injection of the myocardium, and skeletal muscle). The total population was followed for 130.4 patient-years. The study assesses adverse events, common laboratory tests, and long-term follow-up, including incidence of death or development of malignancy. The total group incidence of major adverse events linked to an Ad vector was 0.7%. There were no deaths attributable to the Ad vectors per se, and the incidence of malignancy was within that expected for the population. Overall, the observations are consistent with the concept that local administration of low and intermediate doses of Ad vectors appears to be well tolerated.
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PMID:Safety of local delivery of low- and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of morbid conditions. 1177 12

AIM:To observe the tumor inhibitory effects by transfecting IL-6 cDNA into colon cancer cell line HT-29 with retroviral vector pZIP cDNA.METHODS:Human IL-6 gene was reconstructed in retrovirus vector and transfected into incasing cells PA317 by lipofectamine mediated method, the clones of the cells transferred with hIL-6 were selected by G418,and targeted HT-29 cells were infected with the virus granules secreted from PA317 and also selected by G418.Test gene transcription and expression level by hybridization, ELISA and MTT assay,etc. Analyze tumor inhibitory effects according to the cell growth curve, plating forming rate and tumorigenicity in nude mice.RESULT:Successfully constructed and transfected recombinant expressing vectors pZIPIL-6 cDNA and got positive transfected cell lines. The colon cancer cell line (HT-29 IL-6) transfected with the hIL-6 gene by retroviral vector was estab-lished. The log proliferation period and the doubling time of this cell line was between 4 to 7 days and 2.5 days according to the direct cell count, the cell proliferation was obviously inhibited with MTT assay, the plating inhibitory rate was 50% by plating efficiency test. When HT-29 IL-6 cells were inoculated into the nude mice subcutaneously, carcinogenic activity of the solid tumor was found superior to the control group and the size of tumor was not significantly enlarged. Injection of combination virus fluid containing IL-6 gene into transplantation tumors could inhibit the growth and development of the tumor.CONCLUSION:IL-6 could inhibit the growth and proliferation of colon cancer cells by retroviral vector-mediated transduction.
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PMID:Tumor growth inhibition effect of hIL-6 on colon cancer cells transfected with the target gene by retroviral vector. 1181 30


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