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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There appears to be a natural progression of some preinvasive cervical lesions to more advanced lesions. Although research has evaluated the associations between nutrients and particular preinvasive lesions or invasive disease, little work has been done to compare results across the spectrum of lesions in the progression to invasive disease. This review compiles studies that have evaluated the relation between nutrients and cervical neoplasia and evaluates the general consistency of the literature across stage of disease. Preformed vitamin A does not appear to be related to risk of any preinvasive or invasive lesions, whereas vitamin C has been associated with a reduced risk for dysplasia, in situ cancer, and invasive disease, particularly among smokers. There was evidence of reduced risks associated with various carotenoids and vitamin E at all stages of the disease process, although these studies were inconsistent and further work is needed. Folate was the only nutrient that appeared to be protective for dysplastic lesions and not related to risk of in situ or invasive disease. Red blood cell folate was a better predictor of dysplasia than were serum or dietary folate, and further investigation using this marker of folate status is warranted. Research is needed across a spectrum of lesions within one study, with particular attention to interactions between nutrients and other risk factors for disease.
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PMID:Nutritional epidemiology of cervical neoplasia. 842 98

The purpose of this investigation was to determine whether antitumor selectivity of the third generation thymidylate synthase inhibitor 1843U89 could be enhanced by a combination of the drug with folic acid. The effects of folic acid on toxicity of 1843U89 to the dog and mouse and on antitumor efficacy of 1843U89 in the mouse were studied. These data were compared to the effect of folic acid on the in vitro cell culture antitumor activity of 1843U89. The sensitivity of eight cancer cell lines (three ovarian, one colon, one ileocecal, one epidermoid, one osteosarcoma, and one breast line) to 1843U89 was tested in vitro in the presence and absence of folic acid. Folic acid concentrations greater than 100 microM were required to decrease 1843U89 activity in seven of the cell lines. Only the activity in HCT-8, the ileocecal line, was reserved at folic acid concentrations below 100 microM. Oral folic acid given 30 min prior to an i.v. dose of 1843U89 increased the maximally tolerated dose and the lethal dose of 1843U89, both in dogs and in thymidine-depleted mice. In mice, oral folic acid produced little or no effect upon the antitumor efficacy of 1843U89 in two of three tumor cell lines in vivo. HCT-8, the line that was sensitive to folate reversal in vitro, was also sensitive in vivo. The results show that an oral dose of folic acid 30 min prior to i.v. 1843U89 can block mouse and dog intestinal toxicity without decreasing efficacy of 1843U89 in two of three human tumor lines in the nude mouse. Thus, the data reported here indicate that the antitumor selectivity of 1843U89 may be enhanced through a combination of 1843U89 with oral folic acid.
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PMID:Enhanced antitumor activity for the thymidylate synthase inhibitor 1843U89 through decreased host toxicity with oral folic acid. 852 2

Felt prepared from polyglycolide (PGA) polymer fibers was pasted with fibrin glue for prevention of postoperative pulmonary fistula, and its effects were evaluated. The subjects were 90 patients who underwent thoracotomy and were expected to develop air leakage between March 1990 and the end of 1993. The felt sheet was simply pasted in position in 67 patients, applied and fixed by suturing in 7, and sutured and pasted in 16. The duration of air leakage in the three groups were 4.6 +/- 4.1, 3.9 +/- 4.9, and 3.2 +/- 3.8 days, respectively. According to the surgical procedure employed, the duration of air leakage was 5.0 +/- 4.0 days in 41 patients who underwent pulmonary lobectomy, 5.0 +/- 4.3 days in 5 patients who underwent segmentectomym, 2.6 +/- 3.1 days in 26 cases who underwent partial pneumonectomy, and 4.9 +/- 4.0 days in the 14 cases who underwent bulla resection. In terms of disease, the leakage time was 4.6 +/- 4.2 days in patients with emphysema, 0.6 +/- 1.2 days in those with diffuse pulmonary fibrosis, 0.7 +/- 0.9 days in those with Infectious disease, 4.8 +/- 4.2 in those with lung cancer, 1.5 +/- 1.5 days in those with benign lung tumor, and 3.8 +/- 2.7 days in those with metastatic lung tumors. The procedure had no side-effect on liver or kidney function. No infection was observed even after decortication for empyema. The use of felt prevented excessive shrinking of the lung due to over-suturing. Therefore, intraoperative application of a PGA felt sheet was considered to be an effective method for prevention of pulmonary fistula.
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PMID:[Clinical experience of the combined use of polyglycolide non-woven felt with fibrin glue to prevent postoperative pulmonary fistula]. 853 Aug 38

Recent studies suggest that micronutrients, especially folate, calcium, iron, and antioxidant vitamins, affect the risk of colorectal neoplasia. The objective of this case-control study was to examine the association between these micronutrients and the risk of colorectal adenomas. The study was based on 236 cases with adenomatous polyps or cancer and 409 controls, all colonoscopy patients at University of North Carolina Hospitals between July 1988 and March 1991. After colonoscopy, subjects were interviewed using a semi-quantitative food frequency questionnaire, and average daily nutrient intakes were calculated. Sex-specific odds ratios relative to the lowest quartile of intake for each micronutrient were determined using unconditional logistic regression while adjusting for a number of potential confounders. In women, folate, iron, and vitamin C were inversely related to the risk of adenomas. Folate appeared to be most protective, with women in the highest quartile only 40% as likely to develop adenomas compared with women in the lowest (odds ratio = 0.39, 95% confidence interval 0.15-1.01). In men, greater vitamin E and calcium intakes were associated with reduced risk of adenomas, with vitamin E showing the strongest inverse association. Men in the highest vitamin E quartile had a risk of 0.35 (95% confidence interval 0.14-0.92) relative to those in the lowest. These study results support previous research findings that selected micronutrients protect against colorectal neoplasia.
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PMID:Micronutrients and the risk of colorectal adenomas. 894 32

Folate is an essential cofactor in the generation of endogenous methionine, and there is evidence that folate deficiency exacerbates the effects of a diet low in choline and methionine, including alterations in poly(ADP-ribose) polymerase (PARP) activity, an enzyme associated with DNA replication and repair. Because PARP requires NAD as its substrate, we postulated that a deficiency of both folate and niacin would enhance the development of liver cancer in rats fed a diet deficient in methionine and choline. In two experiments, rats were fed choline- and folate-deficient, low methionine diets containing either 12 or 8% casein (12% MCFD, 8% MCFD) or 6% casein and 6% gelatin with niacin (MCFD) or without niacin (MCFND) and were compared with folate-supplemented controls. Liver NAD concentrations were lower in all methyl-deficient rats after 2-17 mo. At 17 mo, NAD concentrations in other tissues of rats fed these diets were also lower than in controls. Compared with control values, liver PARP activity was enhanced in rats fed the 12% MCFD diet but was lower in MCFND-fed rats following a further reduction in liver NAD concentration. These changes in PARP activity associated with lower NAD concentrations may slow DNA repair and enhance DNA damage. Only rats fed the MCFD and MCFND diets developed hepatocarcinomas after 12-17 mo. In Experiment 2, hepatocarcinomas were found in 100% of rats fed the MCFD and MCFND diets. These preliminary results indicate that folic acid deficiency enhances tumor development. Because tumors developed in 100% of the MCFD-fed rats and because tissue concentrations of NAD in these animals were also low, further studies are needed to clearly define the role of niacin in methyl-deficient rats.
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PMID:Male rats fed methyl- and folate-deficient diets with or without niacin develop hepatic carcinomas associated with decreased tissue NAD concentrations and altered poly(ADP-ribose) polymerase activity. 904 May 40

The cyclopentenone PGs (PGA and PGJ series) inhibit tumor cell proliferation in vitro and tumorigenesis in vivo via mechanisms that are at present poorly understood. The C6 rat glioma cell line synthesizes and secretes insulin-like growth factor-I (IGF-I), which is believed to act as an autocrine factor for these cells. PGA2 inhibits the proliferation of the C6 cells and causes an increase in the fraction of cells in the G1 phase of the cell cycle. The inhibition of cell proliferation by PGA2 is accompanied by a decrease in the abundance of IGF-I messenger RNA (mRNA). This regulation of IGF-I gene expression is specific, as the abundance of hypoxanthine-guanine phosphoribosyl transferase (HPRT) and ubiquitin mRNA is not significantly affected by PGA2. The repression of IGF-I gene expression is observed at PGA2 concentrations as low as 10 microM and is evident within 4 h after treatment of the C6 cells with PGA2. In addition to specifically regulating the expression of the IGF-I gene, PGA2 also decreases the abundance of cyclin D1 mRNA and increases the abundance of Waf1 mRNA. The inhibition of cell proliferation by PGA2 is partially reversed by coaddition of IGF-I, indicating partial dominance of IGF-I action over PGA2 action. To investigate the molecular basis for the regulation of IGF-I gene expression by PGA2, we developed a sensitive RT-PCR assay for IGF-I nuclear transcripts. A similar assay was developed for quantifying HPRT transcripts, which were used as a control. Treatment of the C6 cells with 20 microM PGA2 resulted in approximately a 6-fold decrease in IGF-I mRNA and IGF-I nuclear transcripts. In contrast, HPRT mRNA and nuclear transcript levels were not significantly affected by PGA2. These results indicate that the decrease in IGF-I mRNA abundance that occurs in response to PGA2 is caused largely by a decrease in IGF-I nuclear transcript levels. To identify the cis-acting element that mediates the effect of PGA2 on IGF-I transcription, C6 cells were transiently transfected with IGF-I/luciferase expression constructs in which luciferase transcription is driven by IGF-I P1 promoter fragments extending from -1711 to -328 or from -1114 to +328 relative to the beginning of exon 1. Treatment of cells with PGA2 in these transient transfection assays did not decrease luciferase activity. These results suggest that the cis-acting regulatory element required for the response to PGA2 is located outside the -1711 to +328 promoter interval.
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PMID:Prostaglandin A2 specifically represses insulin-like growth factor-I gene expression in C6 rat glioma cells. 904 99

Folate-conjugated metal chelates have been proposed as potential imaging agents for cancers that overexpress folate receptors. In a previous study, folic acid was linked through its gamma-carboxyl group to deferoxamine (DF), and the 67Ga-labeled complex ([67Ga]DF-folate) was examined for in vivo tumor targeting efficiency in athymic mice with a human tumor cell implant. Although superb tumor-to-background contrast was obtained, slow hepatobiliary clearance would compromise imaging of abdominal tumors such as ovarian cancer. In the present study, folic acid was conjugated to an alternative chelator, diethylenetriaminepentaacetic acid (DTPA), via an ethylenediamine spacer. The desired DTPA-folate (gamma) regioisomer was synthesized by two different approaches, purified by reversed phase column chromatography, and characterized mainly by analytical HPLC, mass spectroscopy, and NMR. In cultured tumor cells, uptake of [111In]DTPA-folate (gamma) was found to be specific for folate receptor-bearing cells, and the kinetics of uptake were similar to those of free folate and other folate-conjugated molecules. In the normal rat, intravenously administered [111In]DTPA-folate (gamma) was found to be rapidly excreted into the urine, giving intestinal levels of radiotracer 10-fold lower than those observed with [67Ga]DF-folate (gamma) at 4 h. In a preliminary mouse imaging study, a folate receptor-positive KB cell tumor was readily visualized by gamma scintigraphy 1 h following intravenous administration of [111In]DTPA-folate (gamma).
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PMID:Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. 932 30

Folate receptor is over-expressed in a variety of carcinomas. To design a cytotoxic drug that would selectively target these carcinomas, we synthesized folate-maytansinoids. These drugs showed high affinity toward folate receptor, appeared to enter cells exclusively via the folate receptor-mediated caveolar pathway and displayed high cytotoxic potency (in the range of 10[-11] to 10[-10] M) and remarkable selectivity for folate receptor-expressing carcinoma cell lines. Folate-maytansinoids represent a new class of tumor-specific agents in which the targeting and the cytotoxic function can be altered independently.
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PMID:Folate-maytansinoids: target-selective drugs of low molecular weight. 939 66

High-affinity receptors expressed on the surface of some tumors can be exploited by chemically conjugating the ligand for the receptor and an antibody against immune effector cells, thus redirecting their cytolytic potential against the tumor. Ovarian carcinomas and some brain tumors express the high-affinity folate receptor (FR). In this report, a transgenic mouse model that generates endogenously arising choroid plexus tumors was used to show that folate/anti-T-cell receptor antibody conjugates can direct infiltration of T cells into solid brain tumor masses. An engineered single-chain Fv form of the anti-T-cell receptor antibody KJ16 was conjugated with folate, to produce a bispecific agent that was substantially smaller than most previously characterized bispecific antibodies. Folate conjugation to the antibody increased T-cell infiltration into the tumors by 10- to 20-fold, and significantly prolonged survival of the mice.
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PMID:Targeting T cells against brain tumors with a bispecific ligand-antibody conjugate. 961 Jul 37

A kit formulation has been developed for convenient, routine compounding of (111)In-labeled In(III)-DTPA-Folate, an investigational radiopharmaceutical for targeting tumor-associated folate receptors. The kit consists of the DTPA-Folate conjugate in sodium citrate solution, from which [(111)In]In-DTPA-Folate can be rapidly and reliably compounded by the addition of aqueous [(111)In]In(III)-chloride.
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PMID:A kit formulation for preparation of [(111)In]In-DTPA-folate, a folate-receptor-targeted radiopharmaceutical. 975 27


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