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

We describe the magnetic resonance (MR) findings in patients with gastrointestinal polyposis syndromes using breath-hold T1-weighted sequences, both standard and with fat suppression, prior to and following gadolinium administration, and breathing-independent single-shot half-Fourier RARE T2-weighted sequences. Six patients with gastrointestinal polyposis syndromes underwent MR examination to investigate for the presence of metastatic disease. The appearances of the gastrointestinal polyps on noncontrast T1-weighted spoiled gradient-echo (SGE), T2-weighted (half-Fourier RARE) images, and early and late gadolinium-enhanced SGE images were determined. Other gastrointestinal findings and extragastrointestinal disease were also evaluated. Patients with the following gastrointestinal polyposis syndromes were included: familial polyposis (n = 3), Peutz-Jeghers syndrome (n = 1), Gardner's syndrome (n = 1), and neurofibromatosis (n = 1). Polypoid lesions in all patients exhibited signal intensity comparable to bowel on noncontrast images and enhanced similar to bowel on early and late gadolinium-enhanced images. Polyps larger than 2 cm, observed in one patient with familial polyposis and the patient with Gardner's disease, showed mild heterogeneity on late gadolinium-enhanced fat-suppressed images. Multiple colonic polyps ranging from 5 mm to 3 cm in diameter were observed in patients with familial adenomatous polyposis. A solitary 1.5 cm polyp associated with entero-enteric intussusception was observed in the patient with Peutz-Jeghers syndrome. Gastric polyps ranging from 5 mm to 6 cm were observed in the stomach of the patient with Gardner's syndrome. Duodenal and jejunal neurofibromas ranging from 1 to 2 cm in diameter were present in the patient with neurofibromatosis. Extra gastrointestinal findings included an adrenal adenoma (1 patient), a pheochromocytoma (1 patient), and liver metastases (2 patients). Gastrointestinal polyps in patients with polyposis syndromes may be visualized on MR images employing breath-hold T1-weighted and breathing-independent snapshot T2-weighted techniques. Appreciation of polyp enhancement on post-gadolinium images is an important finding, which should help distinguish polyps from bowel contents.
 ...
PMID:Polyposis syndromes of the gastrointestinal tract: MR findings. 1067 20

Cyclooxygenase (COX)-2 levels are elevated in several types of human cancer tissues. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the COX-1 and COX-2 protein, the two enzymes that convert arachidonic acids to prostaglandins. Regular use of such NSAIDs significantly reduces the risk and spread of some cancers. The objective of this study was to elucidate the molecular pathology of neoplasms that overexpress COX-2. Epidemiological data and clinical studies were analyzed and compared with results of studies of human tumor tissues, animal models, and cultured tumor cells. COX-2, but not COX-1, is highly expressed in human colon carcinoma, squamous cell carcinoma of the esophagus, and skin cancer. COX-2 is inducible by oncogenes ras and scr, interleukin-1, hypoxia, benzo[a]pyrene, ultraviolet light, epidermal growth factor, transforming growth factor beta, and tumor necrosis factor alpha. Dexamethasone, antioxidants, and tumor-suppressor protein p53 suppress COX-2 expression. COX-2 synthesizes prostaglandin E2 (PGE2) which stimulates bcl-2 and inhibits apoptosis, and induces interleukin-6 (IL-6) which enhances haptoglobin synthesis. PGE2 is associated with tumor metastases, IL-6 with cancer cell invasion, and haptoglobin with implantation and angiogenesis. Drastic reduction in polyp number results from COX-2 gene knockout as well as from selective COX-2 inhibition in a mouse model of human familial adenomatous polyposis. Nonselective NSAIDs, for instance aspirin, and selective COX-2 inhibitors such as celecoxib (SC-58635) and NS-398 suppress azoxymethane-induced colon carcinogenesis in rats. Aspirin, indomethacin, and ibuprofen decrease cultured lung cancer cell proliferation. Selective inhibition of COX-2 is preferable to nonselective inhibition. It reduces cancer cell proliferation, induces cancer cell apoptosis, and spares COX-1-induced cytoprotection of the gastrointestinal tract.
 ...
PMID:Molecular pathology of cyclooxygenase-2 in neoplasia. 1067 79

Wnt signalling is involved in a variety of mammalian developmental processes, including cell proliferation, differentiation and epithelial-mesenchymal interactions, through which they contribute to the development of tissues and organs such as the limbs, the brain, the reproductive tract and the kidney. Wnts are secreted ligands that control cell processes via at least two pathways, one of which, the 'canonical' Wnt signalling pathway, operates through the cytosolic stabilisation of a transcriptional co-factor, beta-catenin. This is achieved by downregulating the activity of a beta-catenin turnover complex. Evidence from tumour expression studies, transgenic animals and in vitro experiments suggests that inappropriate activation of the canonical Wnt signalling pathway is a major feature in human neoplasia and that oncogenic activation of this pathway can occur at many levels. Inappropriate expression of the Wnt ligand and Wnt binding proteins have been found in a variety of human tumours. Further downstream, dysregulation of the beta-catenin turnover complex, by loss of the Adenomatous Polyposis Coli or Protein Phosphatase 2A proteins, or by activating mutations of beta-catenin, has been found in several tumour types, and is believed to be a key step in neoplastic progression. Transcriptional targets of the Wnt pathway include the cellular oncogenes cyclin D1 and c-myc. Activation of the Wnt signalling pathway by various means can therefore be a primary cause in oncogenesis, affecting cell proliferation, morphology and contact inhibition, as well as co-operating with other oncogenes in multistep tumour progression.
Cancer Metastasis Rev 1999
PMID:Wnt signalling in mammalian development and cancer. 1072 85

The Wnt signaling pathway functions reiteratively during animal development to control cell fate decisions. Inappropriate deregulation of this pathway leads to cancer in a number of tissues. The components that transduce the Wnt signal from the cell membrane to the cell nucleus are well conserved between vertebrates and Drosophila. A pivotal Wnt effector is the protein beta-catenin/Armadillo whose stability in the cytoplasm is low in unstimulated cells. Beta-catenin/Armadillo is targetted for proteasome-mediated degradation by a protein complex to which it binds. This complex consists of Axin, a putative scaffold protein which also binds to the tumor suppressor Adenomatous polyposis coli (APC) and glycogen synthase kinase 3 (GSK3)/Shaggy. Wnt signaling somehow inhibits the kinase activity of the quaternary complex. As a consequence, beta-catenin/Armadillo accumulates in the cytoplasm, translocates to the nucleus and becomes a transcriptional co-activator of T cell factor (TCF), the ultimate nuclear target of Wnt signaling. TCF is an architectural protein, mediating the assembly of multi-protein enhancer complexes. It cooperates with other enhancer-binding proteins and, together with beta-catenin/Armadillo, stimulates the transcription of Wnt target genes. Recently, repressors have been identified that prevent TCF from being active in the absence of Wnt signaling.
Cancer Metastasis Rev 1999
PMID:The control of beta-catenin and TCF during embryonic development and cancer. 1072 86

The patient was a 50-yr-old man who had undergone low anterior resection for rectal cancer at the age of 24 yr in 1966. At that time, gastric and colonic polyposis were indicated. Postoperative anastomotic dehiscence occurred and, by 1985, a rectovesical fistula had formed. In 1986, when the patient was 44 yr old, he was examined at our hospital for constriction of the rectum due to the rectovesical fistula. Abdominoperineal excision of rectum and surgical closure of the fistula were performed, and the patient was kept under observation because of a diagnosis of familial adenomatous polyposis. In 1988, when the patient was 46 yr old, early ascending colon cancer was discovered and total colectomy was performed. Then, in December, 1991, gross hematuria was found. Further examination revealed a tumor on the posterior wall of the urinary bladder lumen, and biopsy showed adenocarcinoma. Pelvic recurrence of the rectal cancer was diagnosed, and total pelvic exenteration was performed. There were no distant metastases; histologically, the tumor of the bladder was thought to be due to colonic mucosa of familial adenomatous polyposis that had migrated to the bladder lumen via the rectovesical fistula and had become cancerous.
 ...
PMID:A case of cancerous familial adenomatous polyposis in urinary bladder due to migration of colonic mucosa through rectovesical fistula. 1081 53

Desmoids are uncommon proliferations of fibroblasts that occur with disproportionate frequency in patients with familial adenomatous polyposis. They do not metastasize and are histologically benign. Despite this, the unpredictable and often aggressive nature of familial adenomatous polyposis-associated desmoids and their tendency to occur in intra-abdominal sites means that they present a difficult management problem, and they are a leading cause of death in patients with familial adenomatous polyposis who have undergone colectomy. We report a case of a patient with familial adenomatous polyposis who had extensive and aggressive desmoid disease and whose management was further complicated by a large intrahepatic desmoid. There are no previous reports of desmoids occurring in the liver.
 ...
PMID:Familial adenomatous polyposis complicated by an intrahepatic desmoid tumor: report of a case. 1091 Feb 52

A Japanese woman with familial adenomatous polyposis in whom a duodenal ampullary adenoma underwent malignant change during a 10-year follow-up period is reported. After restorative proctocolectomy in 1989, and extensive small bowel resection for desmoid disease in 1991, regular surveillance duodenoscopies, including three to nine biopsies (mean, 4.8) were performed annually or biannually. Until 1995, the endoscopic findings of duodenal polyposis (including an ampullary polyp) did not progress and the histopathology did not worsen. In 1996, there was an increase in the number and size of the duodenal polyps, and the ampulla of Vater looked enlarged. Open surgery was discussed but not proceeded with because of the risk for short bowel syndrome. In January 1998, she was admitted with a diagnosis of acute pancreatitis. Duodenoscopy and radiological examination revealed that an advanced ampullary cancer had developed, and histopathology revealed a well-differentiated adenocarcinoma. Multiple hepatic metastases and ascites led to her death, in June, 1998. This in-vivo demonstration of the adenoma-carcinoma sequence highlights current limitations in the surveillance and treatment of duodenal lesions.
 ...
PMID:Development of duodenal cancer in a patient with familial adenomatous polyposis. 1108 1

Small intestinal neoplasms are uncommonly encountered in clinical practice. They may occur sporadically, in association with genetic diseases (e.g., familial adenomatous polyposis coli or Peutz-Jeghers syndrome), or in association with chronic intestinal inflammatory disorders (e.g., Crohn's disease or celiac sprue). Benign small intestinal tumors (e.g., leiomyoma, lipoma, hamartoma, or desmoid tumor) usually are asymptomatic but may present with intussusception. Primary malignancies of the small intestine-including adenocarcinoma, leiomyosarcoma, carcinoid, and lymphoma-may present with intestinal obstruction, jaundice, bleeding, or pain. Extraintestinal neoplasms may involve the intestine via contiguous spread or peritoneal metastasis. Hematogenous metastases to the intestine from an extraintestinal primary are unusual and are most typical of melanoma. Because the small intestine is relatively inaccessible to routine endoscopy, diagnosis of small intestinal neoplasms is often delayed for months after onset of symptoms. When the diagnosis is suspected, enteroclysis is the most useful imaging study. Small bowel endoscopy (enteroscopy) is increasingly widely available and may permit earlier, nonoperative diagnosis.
 ...
PMID:Small intestinal neoplasms. 1158 39

We herein present a case of attenuated familial adenomatous polyposis (AFAP) with advanced rectal cancer in a 16-year-old boy. His mother and younger brother both had subcutaneous soft tissue tumors in the back and sparse-type colorectal polyposis. His mother also had dental anomalies and gastric fundic gland polyposis. The patient was admitted to our hospital for investigation of bloody stools. Barium enema and colonofiberscopy revealed advanced rectal cancer and sparse (<50) colorectal polyps. He also had dental anomalies, a subcutaneous soft tissue tumor in the back, and gastric fundic gland polyposis as extracolonic manifestations. A total proctocolectomy and ileoanal anastomosis were performed, and histological examination of the resected specimens confirmed moderately differentiated adenocarcinomas of the rectum with metastases to the regional lymph nodes. The other colorectal polyps were tubular adenomas with no evidence of malignancy. Germline mutations in the APC gene were observed in codons 486, 545, 1493, and 1556. This case serves to demonstrate that a total proctocolectomy with ileoanal anastomosis should be the procedure of choice for young patients found to have advanced rectal cancer associated with FAP.
 ...
PMID:Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case. 1176 74

Cyclooxygenase-2 (COX-2) is the enzyme that normally synthesizes prostaglandins during an inflammatory response. Many primary and metastatic cancers express COX-2, and its presence is correlated with tumor angiogenesis, more invasive tumor phenotype, resistance to apoptosis, and systemic immunosuppression. The expression of COX-2 is associated with a worse prognosis. Inhibition of prostaglandin synthesis may be beneficial in human malignancy. Regular consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of, and mortality rate resulting from, a number of types of gastrointestinal cancers. Premalignant colonic lesions regress following the administration of nonspecific COX inhibitors, such as sulindac (Clinoril). Advanced solid tumor patients treated with indomethacin (Indocin) survive twice as long as do such patients who receive supportive care alone. The U.S. Food and Drug Administration has approved specific COX-2 inhibitors for the treatment of arthritis, pain, and familial adenomatous polyposis. Preclinical studies show that these drugs block angiogenesis, suppress solid tumor metastases, and slow the growth of implanted gastrointestinal cancer cell lines. The COX-2 inhibitors have safely and effectively been combined with chemotherapeutic agents in experimental studies. Ongoing clinical trials are currently assessing the potential therapeutic role of COX-2 inhibitors in both prevention and treatment of a diverse range of human cancers.
 ...
PMID:Celecoxib with chemotherapy in colorectal cancer. 1201 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>