Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.
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PMID:Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice. 1101 69

In 75% of cases, ovarian carcinoma has already metastasized in the abdominal cavity at the time of diagnosis. For determination of the necessity for a supplementary therapy, in addition to surgical resection, it is important to localize and stage microscopical intraperitoneal metastases of the tumor. Intraperitoneal photodetection of tumor metastases is based on preferential tumor distribution of a fluorescent tumor marker. The time-dependent differences in drug concentration between tumor and normal (T/N) tissues can be used to visualize small tumors. We performed fluorescence measurements on abdominal organs and tumor in the peritoneal cavity of rats. 5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was used as the fluorescent marker. Three different drug doses (100, 25 and 5 mg/kg) were used and PpIX fluorescence profiles were followed up to 24 h after intravenous administration. Maximum T/N ratios were found 2-3 h after administration of ALA with all drug doses. A significant T/N tissue contrast was obtained for all abdominal organs tested after administration of 5 mg/kg.
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PMID:Photodetection with 5-Aminolevulinic acid-induced protoporphyrin IX in the rat abdominal cavity: drug-dose-dependent fluorescence kinetics. 1104 24

The results of examination of 47 patients with confirmed diagnosis of cancer of the stomach (21 patients) or 26 suspects were analyzed. 2-4 hours after oral taking of Alasence in the dose 5-10 mg/kg, gastroscopy with spectrofluorescence analysis of ALA-induced protoporphyrin IX was performed. There were no toxic complications due to Alasence taking. The standard spectrodetector LESA-7 was used for fluorescence record registration. The fluorescence spectra were recorded in the range of 650-850 nm. The specific for protoporphyrin IX peak at 700 nm wavelength was analyzed. Fluorescent endoscopic diagnosis allowed to confirm stomach cancer in 21 patients, and to detect cancer in 7 patients, including 2 cases of cancer in situ. The contrast of protoporphyrin IX accumulation (tumor/norm ratio) ranged from 2.5 to 18, that was enough for differential diagnosis in the majority of cases. In analysis of spectrograms for correct contrast calculation it is necessary to take into account the own fluorescence, with was high in some cases.
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PMID:[Spectro-fluorescence analysis of ALA-induced protoporphyrin IX in differential diagnosis of stomach disease]. 1122 Sep 9

Photodynamic therapy (PDT) is a new modality of skin cancer treatment. It involves the administration of photosensitizing drugs which, when localized in tumor tissue can produce its destruction by absorbing an adequate dose of light of an appropriate wavelength. A large number of photosensitizing agents have been tested in PDT experiments. Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is the most commonly used method. 5-ALA is a prodrug converted in situ via the heme cycle into protoporphyrin IX, an effective photosensitizer agent. Treatment of nonmelanoma skin cancers by PDT has met with varying degrees of success. In the case of 5-ALA, this therapy's main limitation is the poor penetration of 5-ALA into skin, due to hydrophilic and charge characteristics. However, the efficacy of 5-ALA-PDT may be improved by (a) development of adequate drug delivery systems; (b) use of enhancers of PpIX production and accumulation in target tissue, and (c) modifications of the 5-ALA molecule. Optimal timing, light sources, doses, and number of applications are also important factors for topical 5-ALA therapy and must be well defined. The aim of this review is to highlight recent progress in 5-ALA-PDT of skin cancer, and to present ways holding promise for its improvement.
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PMID:Photodynamic therapy of skin cancers: sensitizers, clinical studies and future directives. 1130 52

The initiation of mitosis requires the activation of M-phase promoting factor (MPF). MPF activation and its subcellular localization are dependent on the phosphorylation state of its components, cdc2 and cyclin B1. In a two-hybrid screen using a bait protein to mimic phosphorylated cyclin B1, we identified a novel interaction between cyclin B1 and patched1 (ptc1), a tumor suppressor associated with basal cell carcinoma (BCC). Ptc1 interacted specifically with constitutively phosphorylated cyclin B1 derivatives and was able to alter their normal subcellular localization. Furthermore, addition of the ptc1 ligand, sonic hedgehog (shh), disrupts this interaction and allows cyclin B1 to localize to the nucleus. Expression of ptc1 in 293T cells was inhibitory to cell proliferation; this inhibition could be relieved by coexpression of a cyclin B1 derivative that constitutively localizes to the nucleus and that could not interact with ptc1 due to phosphorylation-site mutations to ALA: In addition, we demonstrate that endogenous ptc1 and endogenous cyclin B1 interact in vivo. The findings reported here demonstrate that ptc1 participates in determining the subcellular localization of cyclin B1 and suggest a link between the tumor suppressor activity of ptc1 and the regulation of cell division. Thus, we propose that ptc1 participates in a G(2)/M checkpoint by regulating the localization of MPF.
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PMID:Patched1 interacts with cyclin B1 to regulate cell cycle progression. 1133 87

Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX is a promising tool in bladder-cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumor and normal urothelial cells. RT4 tumor and UROtsa normal urothelial cells were used to simulate a papillary bladder tumor in contrast to normal urothelium. Photodynamically induced damage in plasma membrane and mitochondria was monitored by flow cytometry with propidium iodide exclusion and analysis of aggregate formation of the dye JC-1. Cell morphology was investigated by phase-contrast and fluorescence microscopy following acridine orange staining. Long incubation times (3 hr) led to complete RT4 tumor cell kill accompanied by a marked fraction of damaged normal UROtsa cells. Shorter incubation intervals (1 hr) also resulted in complete RT4 tumor cell kill; however, most UROtsa cells retained their cell properties, including intact plasma membrane and active mitochondria as well as intact cellular morphology. Phototoxicity depends not only on cellular sensitizer accumulation but also on intracellular localization. Analysis of phototoxic mechanisms is an important step for planning combination therapy regimens with, e.g., DNA-damaging agents. Further, data indicate that differential phototoxicity in normal and tumorous urothelium can be enhanced using differences in cellular protoporphyrin IX distribution following short 5-ALA incubation times. These data are encouraging for the in vivo situation since short incubation times are a more practical approach for local photodynamic therapy of early tumor stages not only in the bladder but also, e.g., in the gastro-intestinal tract or bronchial mucosa.
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PMID:Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer. 1134 May 70

Chromosome band 9p21 is a frequent target of homozygous deletion in many tumor types. Putative tumor suppressor genes, CDKN2A (p16), p14(ARF) and CDKN2B (p15), were localized to 9p21. However, there have been reports that suggest that there may be other genes targeted for inactivation in the region. We have developed a method to search for transcribed sequences within large genomic regions. We tested our approach in a 100-kilobase region on 9p21, which is 40 kilobases telomeric to CDKN2A. The method, termed expressed sequence selection (ESS), resulted in the isolation of genomic fragments known to be from 9q21 that are homologous to transcribed sequences. One fragment was used to obtain a 1.2 kilobase cDNA. The sequence of the 5' half of the cDNA was almost identical to exons 3-5 of the MTAP gene, which maps to chromosome band 9p21. The 3' portion of the cDNA had sequence homology to the ALA gene, which maps to chromosome arm 9q. Using Northern blot analysis, the 1.2 Kb cDNA identified several widely expressed transcripts ranging from 1 Kb to 8.5 Kb and displayed a complex pattern of alternative splicing in which certain exons of the 1.2 Kb cDNA are excluded from some of the splice products. Using cancer tissue Northern blots, we could show that all of the transcripts are absent from a leukemia cell line and a lung cancer cell line (K562, A549) with homozygous, genomic deletions within chromosome band 9p21. In addition, the 7 Kb transcript is also absent from two additional tumor cell lines (Molt4, a leukemia derived cell line, and in G361, a melanoma derived cell line) with homozygous deletions. Further investigation will determine whether the difference in the expression pattern between the 7 Kb transcript compared with the other sized transcripts could be due to specific targeting for alteration in certain tumor types.
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PMID:Identification of a 1.2 Kb cDNA fragment from a region on 9p21 commonly deleted in multiple tumor types. 1156 37

Interstitial deletion or loss of chromosome 5, del(5q) or -5, is a frequent finding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for this gene, we identified a candidate, 5qNCA (LOC51780), which lies within a consistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript with a 5286-bp open reading frame which is present at high levels in heart, skeletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML cell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-conserved C-terminus containing a zinc finger with the unique spacing Cys-X2-Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often found in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Preliminary sequence results in AML and MDS samples and cell lines has revealed a possible mutation in the KG-1 cell line resulting in a THR to ALA substitution that has not been found in over 100 normal alleles to date. We propose 5qNCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that further mutational and functional study of this interesting gene is warranted.
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PMID:A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31. 1168 74

Photodynamic therapy (PDT) is the treatment of tumors or dysplasic tissue with drugs that produce cytotoxic metabolites when exposed to light. Aminolevulinic acid HCl (5-aminolevulinic acid HCl; ALA) is a prodrug that is metabolized intracellularly to form the photosensitizing molecule protoporphyrin (PpIX). When PpIX is activated by light, cytotoxic reactive oxygen species and free radicals are generated. ALA can diffuse through skin and preferentially localizes in tumors and dysplasic tissue; subsequent exposure of PpIX-loaded tumor cells to light can destroy the tumor. After application of a 20% solution of ALA to actinic keratosis lesions of the head, PpIX (as measured by skin fluorescence) peaked 11 hours after treatment and the mean clearance half-life was 30 hours. In phase II trials 10 J/cm2 of blue light (wavelength = 417 nm) delivered at 10 mW/cm2 for 1000 seconds was found to provide maximal therapeutic effect on lesions of the head after treatment with 20% ALA. In phase III trials of ALA PDT in 241 patients with lesions of the head 72% of patients had a complete response to treatment at 12 weeks versus 20% of those treated with vehicle and light alone. Some of these patients had been re-treated at 8 weeks. In these trials 12% of ALA-treated patients and 37.5% of those receiving vehicle whose lesions had cleared at 8 weeks had relapsed at 12 weeks. When the total number of lesions were considered the recurrence rate was 5 and 27.9% for ALA- and vehicle-treated lesions, respectively. All patients reported some degree of burning or stinging during PDT but this usually subsided after irradiation was completed and was rarely treatment-limiting. Localized erythema and edema were also common. No other significant adverse effects were noted and treatment was generally well tolerated. A well designed dermal applicator ensured perilesional skin was spared collateral damage.
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PMID:Topical aminolevulinic acid HCl photodynamic therapy. 1170 13

Fluorescence diagnosis aims to improve the management of oral cancer via early detection of the malignant lesions and better delimitation of the tumor margins. This paper presents a comparative study of normal inspection, combined fluorescence diagnosis (CFD) and its 2 main components, autofluorescence and 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence. Biopsy-controlled fluorescence imaging and spectral analysis were performed on a total of 85 patients with suspected or histologically proven oral carcinoma both before and after topical administration of 5-ALA (200 mg 5-ALA dissolved in 50 ml of H(2)0). Fluorescence excitation was accomplished using filtered light of a xenon short arc lamp (lambda = 375-440 nm). As for CFD, a "streetlight" contrast (red to green) was readily found between malignant and healthy tissue on the acquired images. In terms of tumor localization and delimitation properties, CFD was clearly favorable over either normal inspection or its 2 components in fluorescence imaging. The performance of CFD was found to be impeded by tumor keratinization but to be independent of either tumor staging, grading or localization. In spectral analysis, cancerous tissue showed significantly higher PPIX fluorescence intensities and lower autofluorescence intensities than normal mucosa. There is a great potential for CFD in early detection of oral neoplasms and exact delimitation of the tumors' superficial margins and an advantage over white light inspection and each of its 2 main components. The method is noninvasive, safe and easily reproducible.
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PMID:A comparative study of normal inspection, autofluorescence and 5-ALA-induced PPIX fluorescence for oral cancer diagnosis. 1177 71


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