Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 4,184 patients with cancer of the esophagus, 55 second primary cancers were observed, whereas 64 were expected [relative risk (RR) = 0.86]. The absence of an excess risk of alcohol- and tobacco-related cancers was not anticipated. A significant 19% deficit of second cancers was found among 30,843 patients with stomach cancer. Cancer of the rectum, kidney, and lung all occurred significantly below expectation. An excess risk of ovarian cancer (RR = 1.9) was seen in women. Reasons for these findings are not entirely clear. Cancer of the small intestine is rare, and despite a relatively short survival expectation, a moderate excess of second cancers was seen among 868 patients (36 vs. 26.8). Only cancers of the liver and gallbladder were significantly elevated, and the possibility of misclassified metastases is discussed. Colon cancer is one of the most common cancers in Denmark, and 29,490 patients with this disease were at slightly lower risk for development of second cancer (RR = 0.96; 95% confidence interval = 0.9-1.0) than the general Danish population, excluding secondary colon cancers. Esophageal, stomach, and liver cancers occurred less frequently than expected. That cancers of the uterine corpus and ovary were significantly increased supports the notion that common risk factors, such as diet and endogenous hormones, influence the development of these cancers. A significant 23% deficit of second cancers was also found among 26,597 patients with cancer of the rectum, excluding secondary rectal cancer. Significant deficits were seen for cancers of the stomach (RR = 0.5), lung (RR = 0.8), and brain (RR = 0.5), and for multiple myeloma (RR = 0.4). The likelihood of underreporting of second cancers, especially of the digestive system, is discussed. However, cancer of sites previously reported to be associated with rectal cancer, e.g., the colon, breast, and uterus, did not occur below expectation. Cancers of the liver and biliary tract occurred in 4,453 patients; their average survival was only 1 year. Except for a slight excess of cancer of the ovary (5 vs. 1.6), the risk of second cancer development for all sites was consistent with unity (RR = 0.90). The risk of second cancers among 7,752 persons with cancer of the pancreas was not greater than expected (88 vs. 85.2). Males were at significant risk of kidney cancer (RR = 3.2), whereas females showed elevated rates of cancers of the uterine corpus (RR = 3.2) and ovary (RR = 3.1). No site occurred significantly below expectation.
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PMID:Second cancer following cancer of the digestive system in Denmark, 1943-80. 408 3

It may be useful for therapeutic purposes if experimental colonic cancer can be produced in larger animals. Our protocols for experiment to produce colonic cancer in dog were as follows: Two beagle and 12 mongrel dogs were used. Endoscopic examination was done every month or every other month. 1,2-Dimethylhydrazine (DMH) was given subcutaneously in 3 mongrel dogs once a week for 25 months. The protrusion like verruca was observed macroscopically in colonic mucosa in two of them. Histologically it was like lymph follicle hyperplasia in the submucosa. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) soaked in sponge was inserted daily into the rectum of 2 beagle and 2 mongrel dogs for about 20.4 months. A leiomyoma of the colon was detected histologically in one beagle. N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) soaked in sponge was inserted daily into the rectum of 4 mongrel dogs for about 26.5 months. During follow up study, adenoma of the colon was detected by biopsy in one dog. ENNG suppository (containing 50 mg of ENNG) was administered through the anus in 3 mongrel dogs. Colon cancer was induced in all of three dogs. There were metastases to the liver, lung and lymph nodes in one of them. Colonic cancer was successfully induced in dogs by suppository of ENNG into the rectum. This model seems to be the most useful for producing experimental colonic cancer.
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PMID:[Production of experimental colonic cancer in dog. A comparative study of administrative methods of carcinogen]. 667 8

Malignant tumors shed large numbers of cells into the circulation, only a small fraction of which actually produce distant metastases. The cells comprising these tumors may be heterogeneous in many respects including their biological behavior. Inasmuch as colonic epithelial cells secrete mucins that reflect the state of cell differentiation, and differences in mucin structure may be detected by selective lectin binding, we used fluorescein isothiocyanate-conjugated lectins and fluorescence microscopy to analyze mucins secreted by primary colon cancers and metastases. In this way we hoped to determine whether differences exist in the glycoconjugates produced by metastatic and nonmetastatic cell populations. Out studies demonstrated that, in a given primary cancer, the mucin produced differed from that made by its metastases. Thus the vast majority of cells in primary tumors produced mucin that was specifically labeled by fluorescent peanut agglutinin (14 of 16 tumors). In contrast, 72% (37 of 51) of metastatic tumors produced mucin that did not bind peanut agglutinin (p less than 0.001). Colon cancer cells with high metastatic potential may therefore produce mucins that lack an exposed oligosaccharide receptor for this lectin.
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PMID:Characteristics of colorectal carcinoma cells with high metastatic potential. 672 53

Tumors derived from the colonic epithelium exhibit cholesterol metabolism which is clearly different from that in fibroblasts, hepatocytes, adrenals, and ovaries. In hepatocytes and fibroblasts MEV inhibition of the rate limiting step in cholesterol synthesis HMG Co A reductase can be overcome by the uptake of LDL. Colon cancer cells however do not overcome MEV inhibition by LDL uptake but rather exhibit further growth suppression Mevinolin (Mevacor), a drug used to lower serum cholesterol levels has the advantage of accumulating in the liver to approximately 95% with the first pass. A small but variable percentage of non-sterol precursors may escape inhibition and be utilized for other pathways in the isoprenylation of certain proteins, among them members of the ras family. Mutated ras, an oncogene, is found in 40-50% of colon tumors and the expression of a functional gene product is dependent on isoprenylation for anchorage to the tumor cell membrane. d-Limonene, a relatively non-toxic monoterpene found in orange skin oil, selectively inhibits isoprenylation and also accumulates to some extent in the liver. It was hypothesized that the differences in mevalonate metabolism between hepatocytes and colon tumor cells could provide a chemotherapeutic advantage in which MEV and/or d-limonene could effectively inhibit cholesterol synthesis and post-translational modification of proteins with non-sterol cholesterol precursors in colon tumor derived hepatic metastases and thus inhibit their growth. Since each drug affects aspects of mevalonate synthesis at different points, the effects of the combination of their agents on inhibiting tumor metastases was investigated to ascertain if these could be additive. In tissue culture, MEV and d-limonene significantly inhibited the growth of CT-26, a murine transplantable colon tumor. Cholesterol synthesis assessed in these cells indicated that in lipid deficient media the following additions-25-hydroxycholesterol, and LDL significantly reduced cholesterol synthesis. Conversely, perillyl alcohol increased cholesterol synthesis 2.5 fold. In cells cultured in FBS based medium, which have an FBS control, MEV treatment reduced cholesterol synthesis to 65% of control. Perillyl alcohol increased synthesis 1.4 fold and when given in conjunction with MEV, it abolished the effects of this inhibitor. In isoprenylation studies of 14C-mevalonate incorporation into proteins, MEV impaired isoprenylation by restricting synthesis of mevalonate derived intermediates. Results of CT-26 treatment with perillyl alcohol are inconsistent with its putative role as a protein isoprenylation inhibitor. The combination of these agents indicates an additive action which requires additional investigation to elucidate their mechanism(s). Dietary MEV and d-limonene were evaluated alone and in combination for their chemotherapeutic potential in a hepatic "metastasis" model. Using splenic colonization in which CT-26 was implanted into the spleen and ultimately seeded the liver, each of these compounds were found to inhibit the growth of resultant tumors both alone and in combination by approximately 80% versus controls at 35 days post-implantation. Assessment of HMGCoA reductase in liver and tumor indicated that these agents were effective in reaching these target sites. The findings to date indicate that while d-limonene and MEV may differentially affect the same pathway, and their individual actions may appear antagonistic in vitro, their overall action individually or together, appears promising as a chemotherapeutic modality for the possible management of hepatic metastases from colon cancer.
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PMID:Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic "metastases" in vivo. 888 30

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 889 33

Colon cancer with a synchronous ovarian metastasis is occasionally diagnosed at the time of laparotomy for a pelvic mass. The purpose of this retrospective study is to evaluate the clinical presentation as well as the impact of the type of metastatic spread and surgical intervention on overall survival. We reviewed charts of 23 patients treated between 1980 and 1995. Pain was the initial symptom in 14 patients (61%), with only four patients (17%) complaining of rectal bleeding, but with five patients (22%) complaining of uterine bleeding. At the time of laparotomy, the ovarian capsule was intact in 12 patients. Metastatic disease to the peritoneum was seen in seven patients and to the liver in six patients. On pathological evaluation, the median ovarian tumor size was 10 cm, significantly larger than the median colon tumor size of 4.5 cm. Surgical treatment consisted of colon resection in all but one patient, bilateral or unilateral salpingo-oophorectomy in 22 patients, and hysterectomy in nine patients. Only one patient survived 5 years. Sixteen patients died of colon cancer. The median survival time was 17.8 months, ranging from 1 to 86 months. Tumor size was of no prognostic importance. Median survival time of patients with peritoneal disease (10.8 months) was significantly shorter compared to patients without peritoneal disease (25.2 months). In the presence of liver metastasis, the median survival time was, likewise, significantly reduced from 20.1 months to 8.1 months. In conclusion, macroscopic metastatic disease to the ovary is a poor prognostic factor in colon cancer. In selected patients who can be rendered disease-free by surgery, prolonged survival is possible and an aggressive approach is recommended. Survival of patients with peritoneal disease or liver metastasis is short and a mainly palliative approach is recommended.
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PMID:Colon cancer with metastasis to the ovary at time of initial diagnosis. 929 47

Gastrointestinal cancer remains a significant public health threat in developed countries. Even with breath-taking gains in our understanding of the molecular underpinnings of the most common GI cancers, it is clear that the best hope in the foreseeable future lies in the chemoprevention of recurrent cancer and its associated precursors. Colon cancer is an ideal disease for the application of chemopreventive strategies. The molecular biology of colon cancer has been well studied and it is an excellent model for the development of chemopreventive interventions. This fact allows clinical investigators to utilize what is known about discrete biological phases of colon carcinogenesis to tailor clinical trial protocols that may attenuate a future risk for cancer. Among the agents currently in clinical trial testing are anti-oxidants, modulators of metabolism, and antiproliferatives. Current clinical trials have often incorporated the use of biomarkers as intermediate endpoints to assess the efficacy of particular preventives. The current status of ongoing colon cancer prevention trials suggests that this disease, in particular, may well be suited to chemopreventive approaches.
Cancer Metastasis Rev
PMID:Chemoprevention of gastrointestinal cancer. 943 48

The role of reactive nitrogen species (RNS) in colon carcinogenesis is multifactorial and affects diverse processes, such as proliferation, apoptosis, differentiation, tumorigenesis, and metastases. This review describes the stages in colon carcinogenesis where nitric oxide (NO) and inducible NO synthase (NOS2) may influence the progression of a normal mucosa to overt metastatic cancer. Overexpression of NOS2 and an increase in the generation of NO and other RNS may lead to apoptosis resistance, DNA damage, mutation, up-regulation of COX-2, increased proliferation, an increase in oxidative stress and an increase in tumor vascularity and metastatic potential. Therefore, future goals are to establish mechanistically based biomarkers to assess individuals at risk for colon cancer and to implement chemopreventive and dietary strategies that reduce colon cancer risk. An understanding of NO signaling pathways in colon epithelial cells should provide the basis for novel biomarker development. Colon cancer prevention may be achieved effectively by chemically interfering with key components of the NO signaling pathways, changing dietary habits to reduce fat and increase antioxidant-containing vegetables, and dietary supplementation to increase DNA repair.
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PMID:Reactive nitrogen species in colon carcinogenesis. 1123 44

Colon cancer is the third leading cause of cancer death in the United States and the second leading cause in the Northern, Central, and Southern Americas. Appropriate treatment depends on the stage of malignancy, which is determined using the tumor-lymph node-metastases system. In stage III disease, adjuvant chemotherapy increases disease-free and long-term survival following surgery, and chemotherapy is the mainstay of treatment for advanced disease. New therapies are being evaluated, including oxaliplatin, a third-generation platinum analogue approved as first- and second-line therapy for metastatic colorectal cancer in Europe; the drug shows great promise combined with 5-fluorouracil/leucovorin or with irinotecan. The dose-limiting toxicity of oxaliplatin is neurologic, which can be acute or chronic; this can be prevented or reduced in some cases through patient education. Nurses play a critical role in education concerning prevention and management of oxaliplatin-related side effects.
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PMID:New therapeutic options in colon cancer: focus on oxaliplatin. 1199 5

Quantification of circulating cancer cells in whole blood samples by real time quantitative RT-PCR might be of clinical value for monitoring therapeutic effectiveness. In colon cancer patients, carcinoembrynic antigen (CEA) and cytokeratin 20 (CK20) have been frequently used for RT-PCR based tumor cell detection, but the specificity in particular for CEA has been questioned. In this study, we compared real-time RT-PCR for CEA and CK20 and analysed patients with metastatic disease (n=32) and healthy volunteers (n=17). CK20 mean values were elevated in cancer patients (P<0.001) and defined a subgroup (38%) who showed CK20 levels at least 100-fold above the highest value of the healthy control group. In contrast, only two cancer patients (6%) showed elevated CEA levels. Samples of the healthy control group showed exclusively a CEA-PCR product of 79 degrees C melting temperature. Thirty per cent of the colon cancer patients showed an additional product of 82 degrees C melting temperature. The 82 degrees C product was identical with the amplification product of CEA-cDNA and cDNA from different colon cancer cell lines. Colon cancer cells were spiked into normal blood in 10-fold dilutions that resulted in a dose dependent shift of the melt curve from 79 degrees C to the 82 degrees C. Sequencing of the PCR products showed that white blood cells express a splice variant of CEA, which hinders detection of tumor cell cDNA in whole blood samples. Our findings have implications for the use of CEA as a diagnostic molecule (e.g. by RT-PCR). The discovery of a physiologically expressed CEA splice variant might lead to a better understanding of the biological function of CEA and its family members.
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PMID:Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells. 1242 Feb 18


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