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)

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in host antitumor immunity. For example, high levels of tissue PGE2 are frequently associated with suppression of immune surveillance and killing of malignant cells. Conversely, immune responses are generally enhanced by drugs that inhibit prostaglandin synthesis. PGE2 can act as a feedback inhibitor for cellular immune processes, such as T-cell proliferation, lymphokine production, and cytotoxicity. This effect is also seen for macrophage activity and natural killer cell toxicity. In general, either increased production of PGE2 or increased sensitivity to normal amounts of PGE2 results in depressed cellular immunity. Cyclooxygenase inhibitors (NSAIDs) such as piroxicam which decrease PGE2 production can stimulate cellular immune function both in vitro and in vivo. A variety of tumor cell lines and human malignancies produce large quantities of prostaglandins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention. 130 81

Ornithine decarboxylase (ODC), a key enzyme in mammalian polyamine biosynthesis, has been proposed to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. We investigated the basal levels of ODC activity in sigmoid and rectal mucosae, and basal and tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced levels of skin ODC activity in individuals with a personal history of colon cancer (n = 9 colon; n = 58 skin), a family history of nonpolyposis hereditary colorectal cancer (n = 49; n = 42), adenomas (n = 16; n = 40), and healthy, family history-negative control subjects (n = 40; n = 79). Using a fresh tissue assay and samples obtained after a standard colon lavage preparation, colon mucosal ODC levels ranged from 0 to 192 pmol/mg/h (sigmoid, 0-163 pmol/mg/h; mean, 36 +/- 32 pmol/mg/h; rectum, 0-192 pmol/mg/h; mean, 35 +/- 32 pmol/mg/h). No differences among the four groups of subjects were found for either colon or skin ODC levels, and there were no sex differences overall or in any group. These results are not compatible with the suggestion that ODC levels are a useful marker of risk for colorectal cancer.
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PMID:Levels of colorectal ornithine decarboxylase activity in patients with colon cancer, a family history of nonpolyposis hereditary colorectal cancer, and adenomas. 130 5

Monoclonal antibody drug conjugate A7 was prepared from a mouse splenocyte immunized against human colon cancer. A7 reacted with 80 percent of colorectal cancer and pancreatic cancer. A7 was bound covalently to neocarzinostatin (NCS) to form A7-NCS. A7-NCS had strong cytotoxic activity in vivo and in vitro study. A total of 77 patients with colorectal cancer, including the patients with liver, lung and peritoneal metastasis, were treated with A7-NCS. There were some tumor reduction of liver metastasis on CT scan and pain relief. Follow up study of colorectal cancer patients treated with monoclonal antibody drug conjugate A7-NCS was carried out, with comparing to those treated conventional chemotherapy. Survival rate of the patients with postoperative liver metastasis treated with A7-NCS was slightly higher than that of the patients treated with conventional intraarterial infusion chemotherapy. There was no difference between the group treated with A7-NCS and that treated with conventional chemotherapy in the overall postoperative survival. Patients given a higher dose of the conjugate had a higher survival rate. There were no serious adverse effects in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all A7-NCS treated patients.
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PMID:Monoclonal antibody-drug conjugate therapy for the patients with colorectal cancer. 130 22

The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.
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PMID:Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. 131 68

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.
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PMID:p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. 131 70

The effect of dietary supplementation with pectin and/or guar gum on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 120 male Sprague-Dawley rats. The rats were given a weekly injection of DMH for 8 weeks and were maintained on a basal fiber-free diet supplemented with 5% cellulose. The rats were then subdivided into four groups and kept on the basal fiber-free diet supplemented with either no fiber, 10% pectin, 10% guar gum or a combination of 5% pectin/5% guar gum for a period of 24 weeks. The 8 weeks of DMH administration were defined as the initiation stage of carcinogenesis and the next 24 weeks were defined as the promotional stage of carcinogenesis. Food and water were available ad libitum. The rats were killed 32 weeks after the start of the experiment and tumor incidence, location and frequency in the colon were determined. Other parameters measured were body weight and caloric intake. Dietary fiber supplementation with 10% pectin or with 10% guar gum but not with the combination of 5% pectin/5% guar gum (fed during the promotional stage of carcinogenesis), was found to suppress colon cancer incidence to a significant extent.
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PMID:Dietary supplementation with pectin and guar gum on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. 131 14

Bombesin (BBS) exerts significant effects on the growth of a mouse colon cancer cell line (MC-26) in vitro. The presence of specific binding sites on MC-26 cells for gastrin-releasing peptide (GRP)/BBS-related peptides was recently reported by us. In the present study, we determined that the transcript size of the mRNA species that codes for GRP receptors is 9 kilobase pairs, which is similar to that reported for mouse Swiss 3T3 cells, using the complementary DNA probe for the GRP receptor gene from mouse Swiss 3T3 cells. We next examined the effects of potent GRP receptor antagonists, D-Phe6, bombesin(6-13)-propylamide (D-Phe6,BN(6-13)PA) and Leu13-psi-(CH2NH)Leu14-bombesin (LL-BBS), on BBS-stimulated growth of MC-26 cells in vitro. A possible autocrine role of GRP in the growth of MC-26 cells was also investigated. MC-26 cells were inoculated s.c. into male BALB/c mice, and tumors were harvested 21-28 days postinoculation. Both D-Phe6,BN(6-13)PA and LL-BBS significantly inhibited the binding of 125I-GRP to MC-26 tumor membranes in a dose-dependent manner, with 50% inhibitory concentrations of 4.5 +/- 0.52 nM and 87 +/- 6 nM, respectively. D-Phe6,BN(6-13)PA similarly inhibited the specific binding of 125I-GRP, cross-linked to a approximately 80 kilodalton binding protein on the MC-26 tumor membranes. In order to determine whether the BBS receptor antagonist, D-Phe6,BN(6-13)PA, functioned as an antagonist or an agonist of biological functions, we measured the bioefficacy of D-Phe6,BN(6-13)PA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A potent bombesin receptor antagonist inhibits bombesin-stimulated growth of mouse colon cancer cells in vitro: absence of autocrine effects. 132 98

The three ras genes code for proteins with a putative role in cellular signal transduction. They belong to a larger family of small guanosine-triphosphate (GTP)-binding proteins. The ras proteins acquire transforming activity when amino acids are substituted at one of a few specific sites, as a result of a point mutation in the gene. In about one third of adenocarcinomas of the lung, a K-ras mutation is present in codon 12 of the gene. Patients with early stages of K-ras mutation-positive tumors have a very unfavorable prognosis, even if apparently radical resection of the tumor has taken place. K-ras mutations are very rare among nonsmokers, and it is reasonable to assume that carcinogens in tobacco smoke directly cause the mutation. The types of ras mutations found in lung cancer are different from those in gastrointestinal malignancies. Colon cancer is mainly associated with mutations leading to substitution of the normal glycine at amino acid position 12 of K-ras by either valine or aspartic acid, and mutations in N-ras are not exceptional. In contrast, the predominant mutation in lung cancer leads to substitution of cysteine in codon 12. Several other members of the ras gene superfamily are also expressed in human lung cancer, but a possible relationship with lung tumorigenesis remains to be established.
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PMID:The ras gene family in human non-small-cell lung cancer. 132 34

The enzyme D-galactose oxidase (GO) oxidizes the carbon-6 position of the hydroxyl groups of galactose-N-acetyl galactosamine, which are commonly present in colon cancer cells and in rectal mucin of patients with colon cancer. We have studied the marker disaccharide galactose and N-acetylgalactosamine on tissue sections by the GO-Schiff reagent in normal, preneoplastic, and neoplastic human colorectal epithelial and compared it with peanut agglutinin reactivity. Fifty-seven (81.4%) of 70 carcinomas, 83.3% (10/12) of precancerous lesions, 50% (10/20) of the mucosa remote from cancer, and 58.1% (25/43) of the mucosa immediately adjacent to cancer showed a positive reaction with GO-Schiff, but the normal control mucosa was nonreactive. The GO-Schiff reagent showed an intense reactivity with mucinous adenocarcinomas and poorly differentiated adenocarcinomas. An intense reactivity was also seen in the intracellular mucus of abnormal dilated crypts (polyps, five of five cases; colitis, four of seven cases; and remote mucosa, 10 of 20 cases). Comparison of peanut agglutinin and GO-Schiff reactivity showed that the nonmucinous (glandular) adenocarcinomas less frequently reacted with the GO-Schiff sequence. Our results showed that the carbohydrate moiety detected by the two techniques may not necessarily be the same, warranting further biochemical analysis. Meanwhile, the data suggested that, like peanut agglutinin, the GO-Schiff sequence has the potential to identify the tumor marker either at the tissue level or by a mucin test for screening colorectal cancer or precancer.
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PMID:Detection of the tumor marker D-galactose-beta-(1-->3)-N-acetyl-D-galactosamine in colonic cancer and precancer. 133 46

Like calcium, vitamin D may protect against colorectal neoplasia as it reduces epithelial cell proliferation and induces differentiation. Although its therapeutic use is limited by its effects on calcium metabolism, analogues such as calcipotriol produce little hypercalcaemia. Stathmokinetic and immunohistochemical techniques were used to study the effect of 1,25 (OH)2 D3 and its analogues on cell proliferation in human rectal mucosa and a colon cancer cell line. Paired sigmoidoscopic biopsy specimens were obtained from 17 control patients and five patients with familial adenomatous polyposis. Explants were established in organ culture, with or without the addition of vitamin D. Proliferation was assessed using (1) metaphase arrest to determine the crypt cell production rate (CCPR) and (2) Ki-67 monoclonal antibody directed against an antigen present in proliferating cells. 1,25 (OH)2 D3 in concentrations of 1 microM-100 pM (10(-6)-10(-10) M) reduced the CCPR (cells/crypt/hour) from 4.74 to 2.15-2.67 (p < 0.001), and the Ki-67 labelling index from 7.28-3.74 (p < 0.01). Likewise, vitamin D2, 10 nM (10(-8) M) reduced the CCPR from 4.74-2.74 (p < 0.05) and calcipotriol from 4.86-2.38 (p < 0.05). In familial adenomatous polyposis patients 1,25 (OH)2 D3 100 pM (10(-10) M) halved the CCPR from 8.75-4.22. Calcipotriol (10(-5) M to 10(-9) M) produced a clearcut dose response inhibition of HT-29 cell growth. Thus, vitamin D and its metabolites inhibit proliferation in normal and premalignant rectal epithelium and suppress growth in a colorectal cancer cell line.
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PMID:Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. 133 58


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