Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human transformed T cell lines were able to induce polyclonal B cell activation and immunoglobulin (Ig) secretion from peripheral blood mononuclear cells, spleen cells and tumor-infiltrating lymphocytes (TIL). Cells from one of the lines tested, MOT, did not require any exogenous stimuli to induce maximal responses and under similar conditions induced higher levels of response than peripheral blood T cells or other T cell lines. MOT-induced B cell activation and Ig secretion required cell contact and factors present in the MOT culture supernatant. MOT cells induced B cell responses from TIL in the three tumors tested (melanoma, ovarian and colon cancer) and HIV-specific immunoglobulin secretion by spleen cells from an HIV+ patient.
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PMID:The use of transformed T cell lines for clonal expansion of human B cells from peripheral blood, spleen, and tumor-infiltrating lymphocytes. 845 98

The thymidine analogue zidovudine is currently used for the treatment of HIV-infected patients, as the early development of the drug as an anticancer agent yielded modest results. A comprehensive preclinical analysis, however, showed that inhibitors of de novo thymidylate synthesis, including fluorouracil and methotrexate, enhanced the antiproliferative activity of zidovudine in cancer cells. Significant inhibition of tumour growth was obtained in mice bearing human colon cancer xenografts and given intraperitoneal zidovudine 300 to 600 mg/kg weekly in combination with methotrexate 87.5 mg/kg or intraperitoneal fluorouracil 85 mg/kg, and in pharmacokinetic studies high peak drug plasma concentrations (Cmax) of zidovudine were obtained, ranging from 610.3 to 1698.8 mumol/L. In order to exploit the therapeutic activity of zidovudine, phase I and II clinical studies were designed in combination with fluorouracil and the pharmacokinetic-pharmacodynamic profile of zidovudine was investigated. Clinical responses were obtained in patients treated intravenously with bolus fluorouracil 500 mg/m2, leucovorin and short (90 to 120 minutes) infusions of high dose zidovudine (up to 10 g/m2), generating drug Cmax similar to those obtained in preclinical models. However, in chemotherapy-pretreated patients receiving high dose zidovudine by the oral route (1 to 9 g/m2/day) or 48-hourly continuous intravenous infusion (2 to 20 g/m2/day) in combination with fluorouracil and leucovorin, treatment failures were observed despite high systemic exposure, described as the area under the plasma concentration-time curve and the occurrence of DNA strand breaks in peripheral blood mononucleated cells, the biological expression of zidovudine activity. In conclusion, preclinical and clinical evidence suggest that the schedule of administration of zidovudine is a requisite for the expression of its activity, indicating the importance of concentration-monitored trials to optimise chemotherapy dose administration in patients. The likelihood of tumour response appears to be related to the achievement of high peak plasma concentrations of zidovudine, and constant infusions appear less likely to produce clinical results.
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PMID:Pharmacokinetic optimisation of the treatment of cancer with high dose zidovudine. 951 87

A survey sponsored by the Interamerican Association of Gastroenterology (AIGE) related to decision making in conflictive ethical situations in the setting of gastroenterological practice was designed (AJ-JCG). Seven problem-cases with 3 to 5 pre-established and not-excluding answers each, demographic and occupational data were included, by public invitation during 1996-97 AIGE educational activities in La Plata (Argentina), Montevideo (Uruguay) and Santo Domingo (Dominican Republic). Data were inserted in a computerised data base, and chi square, Fischer and Maentel-Henzel tests were used for statistical studies. 118 out of 460 doctors registered to educational activities answered at the survey (25.6%). Mean age was 42 +/- 15 years and 57.6% were male; 48.5% were under 10 years of professional practice and 19.5% were over 20 years. Gastroenterology was the main specialty in 89.8%. Although only 15.2% of participants reported as not having Ethical Committee (EC) in their institutions, the option of consulting was not very frequently selected, except in cases of request about pregnancy interruption in the HCV infected mother (22.9%), inclusion of the young alcoholic cirrhotic man in the waiting list for liver trasplant (17.8%), and the Jehova's Witness conscious patient with bleeding esophageal varices (13.5%). Cases of direct communication to the patient of early colon cancer diagnosis (66.1%), and inclusion of the young end stage alcoholic cirrhotic patient in the waiting list for liver trasplantation (65.2%), had the higher consensus. On the other hand, lower consensus (39%) was seen in the case of variceal bleeding in the encephalopathic Witness of Jehova patient. Differential criterla were observed related to sex: 38% of women versus 14.7% of men (p < 0.01) refuse the interruption of pregnancy to the infected HCV patient because of personal convictions against abortion. In the case of suspected HIV co-infection in the IVD HBsAG + carrier, 46% of women vs. 27.9% of men (p < 0.05) indicate HIV screening test without any explanation to the patient because "he could transmit a fatal disease". In this same case, time from graduation was related to differences in option selection: 80.9% in the group > 20 years of professional exercise asked for patient consent and accepted his decision, versus 52.7 and 27.5% in 0-9 and 10-19 years group respectively (p < 0.05). Usual medical and social worries as communication (truth, informed consent), the autonomic decision of biological death versus the sacrament of life, justice in allocation resources, confidentiality and social concern, abortion, and many other controversies linked to tecno-scientific development, impact the practice of Gastroenterology in latinoamerican countries. However medical answers to ethical dilemmas are not uniform. Although our results ought to be verified by other studies they clearly suggest the needs for systematic incorporation of applicated Ethics in pre and postgraduate Gastroenterology curricula, besides the regular activities of our regional institutions.
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PMID:[Ethical dilemmas in gastroenterology practice in Latin-American countries: the AIGE survey]. 1049 18

The success of IL-2 gene therapy in cancer is in part dependent on the development of high level IL-2 gene expression vectors. Currently, expression vectors based on the human cytomegalovirus (CMV) promoter give the highest levels of expression. We have attempted to construct new IL-2 expression vectors to test whether gene expression can be further increased. The first approach was to use the new SR-alpha promoter to control IL-2 gene expression. The second approach was to combine the Tat transcription activator gene and the HIV 1 and 2 promoters in the same construct so that the levels of gene expression can be amplified. Transient transfection results using the human colon cancer cell line SW480 showed that the SR-alpha promoter yields similar levels of activity as the CMV promoter. However, the HIV 1 and 2 promoter-based amplifier constructs produced 11 and 28 times more secreted IL-2 than the CMV promoter control. The augmented activity of the amplifier constructs was dependent on the presence of the Tat gene and the transcriptional units must be placed in the same orientation. Reducing the size of the vectors by elimination of the neomycin selectable marker did not increase the activity of the constructs.
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PMID:Construction of new amplifier expression vectors for high levels of IL-2 gene expression. 1067 73

Based on general SARs previously described for anti-HIV-1 diarylsulfone derivatives, a series of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes has been prepared and evaluated as potential antiviral and antitumor agents. In cell culture, some of the 2-aminothiophenes exhibited moderate and selective activity against HIV-1, with 2-amino-3-(2-nitrophenylsulfonyl)thiophene (7e) being most attractive (EC(50)=3.8 microg/mL, CC(50)=>100 microg/mL). In broad-spectrum antiviral assays, the 3-arylsulfonyl-2-(trifluoroacetamido)thiophenes (8c-g) and 2-acetamido-3-arylsulfonyl-5-nitrothiophenes (9f-g) proved considerably active (IC(50)=0.1-10 microg/mL) against human cytomegalovirus (CMV) and/or varicella zoster virus (VZV). Based on the activity of the trifluoroacetamides, ring-modified furan, N-(substituted)pyrrole, phenyl, and 3,4-thiophene analogues were prepared, and these compounds were also active against CMV and/or VZV, with the notable exception of the 3,4-thiophene derivative. In contrast to other amines, the 2-aminopyrrole precursors (13a-d) also exhibited potent activity against CMV. Unfortunately, most of these compounds displayed significant cytotoxicity against human fibroblasts, the cells supporting CMV and VZV replication, and thus selectivity indices were low. The most notable exception to this was the naphthyl-substituted aminopyrrole 13d, which exhibited both potent (IC(50)=0.3 microg/mL) and selective (CC(50)=>50 microg/mL) activity against CMV. Finally, thiophene aryl amides 8i-k displayed moderate in vitro activity against certain leukemia, breast, and colon cancer cell lines.
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PMID:Synthesis and antiviral/antitumor evaluation of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes and related compounds as a new class of diarylsulfones. 1137 70

On the basis of the bioisosteric rationale to apio dideoxynucleosides, novel thioapio dideoxynucleosides have been synthesized, starting from 1,3-dihydroxyacetone via thioapio sugar acetate as a key intermediate. The intermediate was condensed with silylated pyrimidine bases such as N(4)-benzoylcytosine, uracil or thymine in the presence of TMSOTf to give the beta-anomers and alpha-anomers, respectively. The intermediate was also condensed with silylated 6-chloropurine to give the 6-chloropurine derivatives and which were converted to adenine derivatives and, N(6)-methyladenine derivatives and, and hypoxanthine derivatives and, respectively. The guanine analogues and were also synthesized from the condensation of sugar acetate with 2-acetamido-6-chloropurine. All synthesized final compounds were tested against HIV-1. Most of the synthesized compounds exhibited toxicity-dependent anti-HIV-1 activity, among which 6-chloropurine derivative was found to be the most cytotoxic and showed good cytotoxicity against colon cancer cell lines. Although we could not find good anti-HIV agents in this study, findings of some anticancer activity in this series will allow this class of nucleosides to be the new template for the development of new anticancer agents (Fig. 1).
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PMID:Synthesis and biological evaluation of novel thioapio dideoxynucleosides. 1188 12

Probiotics are defined as live microorganisms of human origin. Their use may favorably influence human health and ameliorate or prevent certain diseases. Prebiotics are non-digestible foodstuffs (fiber, oligofructans - "colonic foods"), which enter the colon and are metabolized by the probiotics. Probiotics should fulfill the following criteria: Phenotypic and genotypic classification, no pathogenic properties, human origin, application in the living state, resistance to gastric acid and bile, ability to adhere to colonocytes, ability to colonize the gut, clinically proved favorable health-effect, and safety. Experimental and clinical studies supplied evidence of the possible use of probiotics in the following diseases: Traveler's diarrhea, antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, infantile diarrhea, rotavirus enteritis, inflammatory bowel disease, irritable bowel syndrome, colon cancer, peritonitis, acute pancreatitis, and diarrhea associated with HIV infection. Probiotics displayed the following effects in these studies: Involvement in production of essential nutrients of the colonic mucosa, beneficial effect on intestinal immunity, recovery of the disturbed gut mucosal barrier and prevention of microbial translocation, elimination of toxins and eradication of microbial pathogens, production of steroids from cholesterol and reduction of its pool in circulation, participation in regulation of intestinal functions, reduced incidence of chemically induced colon tumors in rodents. Probiotics open new therapeutic modalities in a number of diseases and it may be expected that their importance will increase with growing knowledge and experience.
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PMID:[Probiotics in gastroenterology]. 1190 55

Since the advent of HAART, the natural history of HIV disease has been changing, with decreased risk of life-threatening opportunistic infections and prolonged survival. Concurrently, a variety of non-AIDS-defining cancers have been reported with increased incidence in HIV-infected adults, including anal cancer, Hodgkin's disease, head and neck cancer, testicular cancer, lung cancer, colon cancer, basal cell cancer, squamous cell cancer of the skin, and melanoma. It appears that these tumors may have a more aggressive clinical course in HIV-infected people. Available data, however, suggest that antitumor response and survival in HIV-infected people with malignancy are improved in people with higher CD4 counts. The possible mechanisms for the increased incidence and altered clinical course of these malignancies in HIV-infected people remain unclear.
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PMID:Non-AIDS-defining cancer in HIV-infected people. 1285 61

There has been heightened legislative attention to medical privacy and to protections from genetic discrimination, without large-scale studies to document privacy concerns or analysis of whether experiences differ by whether the condition is genetic (defined here as a single-gene disorder) or non-genetic. To determine whether experiences regarding privacy, disclosure, and consequences of disclosure differ by whether one's medical condition is genetic, we conducted a descriptive study with one-time, structured quantitative and qualitative interviews. We interviewed approximately 100 adults or parents of children with each of the following medical conditions: sickle cell disease, cystic fibrosis, diabetes, and HIV, and 200 adults with or at risk for breast cancer or colon cancer. The percentages of the total 597 respondents experiencing positive or negative consequences of disclosure and the degree to which experiences differed by whether the condition was genetic were the outcomes of interest. Seventy-four percent were glad and 13% regretted others knew about their condition; these findings did not differ significantly by genetic vs. non-genetic condition. Reports of job and health insurance discrimination were not uncommon for the overall study population (19 and 27%, respectively) but were more likely among those with genetic conditions (30 and 37%, respectively). Legislation and other policy-making should target the needs of persons with all conditions and not focus exclusively on genetic discrimination, given that experiences and concerns generally do not differ based on the genetic etiology of the condition.
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PMID:Medical privacy and the disclosure of personal medical information: the beliefs and experiences of those with genetic and other clinical conditions. 1521 47

A case of a 38 year-old male patient, from Lima, with a three-year period illness, characterized by abdominal pain, diarrhea, ponderal weight loss and fever is showed. He is examined by colonoscopy, with endoscopic diagnosis of colon cancer and undergoes surgery. The histopathological diagnosis was severe acute and chronic ulcerative ileocolitis, suggesting Crohn disease. A month later he again showed abdominal pain, diarrhea and fever, so a new colonoscopy is performed revealing multiple ileum ulcers and in the anastomotic area. The biopsy revealed an acute and chronic inflammatory process. The colon radiography showed a filling defect and irregularity in the cecum, and the upper endoscopy revealed esophageal ulcers. In addition, a number of analyses were carried out, such as: coproculture, HIV, and VK on sputum and feces, as well as CEA dosage, resulting all of them negative. The thorax radiography was also normal.He was diagnosed with Crohn's disease and was treated with mesalacin. Evolution was fast, showing weight gain, which allowed the discharge of the patient from the hospital seven (7) days later. The anatomical pathology never did confirm the final diagnosis, which brings us to the question:Are the granulomas always necessary for the final diagnosis of Crohn's disease?
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PMID:[Are granulomas necessary for the final diagnosis of Crohn disease?]. 1524 96


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