Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration.
 ...
PMID:Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system. 889 42

Gastroesophageal reflux is a very common disorder. Typical symptoms are heartburn, regurgitation and chest pain. Recently, it has been demonstrated that gastroesophageal reflux may generate or worse extraesophageal symptoms such as asthma, chronic bronchitis, posterior laryngitis, and chronic cough. The diagnosis of gastroesophageal reflux is suggested by typical symptoms which improve under a therapy with proton pump inhibitors. pH-monitoring over 24 hours is able to establish directly the diagnosis by measuring acid reflux into the esophagus. Manometry detects the two most common causes of gastroesophageal reflux: insufficiency of the lower esophageal sphincter or esophageal motility abnormalities. Gastroesophageal reflux can lead to reflux esophagitis, which is diagnosed endoscopically. An endoscopy should routinely be performed in case of dysphagia, anemia, or loss of weight. A long-term sequela of gastroesophageal reflux is the development of Barrett's-esophagus, a condition which has to be verified by endoscopy and biopsy. This premalignant lesion is defined by a metaplastic change from the normal squamous mucosa to a specialized intestinal epithelium characterized by goblet cells. Because dysplasia in these metaplastic areas can lead to esophageal adenocarcinoma, regular endoscopic surveillance with biopsies is recommended. Gastroesophageal reflux can significantly impair the quality of life and can cause complications that include the neoplastic progression from Barrett's esophagus to carcinoma. Therefore, appropriate diagnostic procedures and adequate therapy are required. This article summarizes the diagnostic approach to patients with gastroesophageal reflux, reflux esophagitis and Barrett's-esophagus. The impact of endoscopy, pH-monitoring, esophageal manometry, radiology and scintigraphy are reviewed.
 ...
PMID:[Diagnosis of gastroesophageal reflux and Barrett esophagus]. 1092 25

NETs of pancreas are rare and may or may not be associated with symptoms of hormone overproduction. Treatment is required for control of tumor growth and for relief of symptoms associated with excess hormone. With advances in the nonsurgical management of many hormone-related symptoms (e.g., proton pump inhibitors or somatostatin analogues), care for many of these patients has shifted toward the control of tumor progression. Complete surgical resection is the only curative treatment for these tumors. With improvements in the preoperative imaging and intraoperative localization techniques, it is hoped that these tumors will be identified and resected for cure with increased frequency. For patients with hepatic metastasis, initial expectant observation and medical management of symptoms is appropriate in view of the long and indolent course of the disease. Hepatic arterial embolization is the preferred mode of palliation for pain and hormonal symptoms. A curative hepatic resection may be possible in selected patients.
 ...
PMID:The surgical management of pancreatic neuroendocrine tumors. 1145 68

Neoplastic progression in Barrett's esophagus is a multi-step process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasia-carcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett's esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-fixed, paraffin-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27(kip1) protein, but did not display appreciable nuclear staining for p16(kip4), p21(cip1) or cyclins D1 and E. Barrett's metaplastic specimens displayed increased expression levels of p16(kip4) (74%), p21(cip1) (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a significant correlation between the expression of p16(kip4) and cyclin E, and p21(cip1) and p27(kip4) with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett's esophagus. Treatment with proton pump inhibitors appears to alter this increased expression.
 ...
PMID:Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus. 1175 81

Multipolar electrocoagulation (MPEC) is a readily available technique that can be applied for endoscopic ablation of Barrett's esophagus. MPEC, in combination with high dose proton pump inhibitor therapy or antireflux surgery, results in normal squamous epithelium in most patients without major adverse effects. The ultimate clinical role of MPEC has not been determined but may be adjunctive to other techniques in appropriately selected patients at high risk for neoplastic progression.
 ...
PMID:Multipolar electrocoagulation. 1462 1

Barrett's oesophagus is a frequent complication of gastro-oesophageal reflux disease predicting oesophageal adenocarcinoma. The majority of Barrett's patients will not develop cancer, so that specific methods of identification of those at risk are required. Recent molecular studies have identified a selection of candidate biomarkers that need validation in prospective studies. They reflect various changes in cell behaviour during neoplastic progression. The ASPECT trial in the UK aims to establish whether chemoprevention with aspirin and a proton pump inhibitor will reduce adenocarcinoma development and mortality in patients with Barrett's oesophagus. It will also validate biomarkers for progression and clinical response and further study disease pathogenesis.
 ...
PMID:Molecular changes in the progression of Barrett's oesophagus. 1767 46

Endocytosis and trafficking of receptors and nutrient transporters are dependent on an acidic intra-endosomal pH that is maintained by the vacuolar H(+)-ATPase (V-ATPase) proton pump. V-ATPase activity has also been associated with cancer invasiveness. Here, we report on a new V-ATPase-associated protein, which we identified in insulin-like growth factor I (IGF-I) receptor-transformed cells, and which was separately identified in Caenorhabditis elegans as HRG-1, a member of a family of heme-regulated genes. We found that HRG-1 is present in endosomes but not in lysosomes, and it is trafficked to the plasma membrane upon nutrient withdrawal in mammalian cells. Suppression of HRG-1 with small interfering RNA causes impaired endocytosis of transferrin receptor, decreased cell motility, and decreased viability of HeLa cells. HRG-1 interacts with the c subunit of the V-ATPase and enhances V-ATPase activity in isolated yeast vacuoles. Endosomal acidity and V-ATPase assembly are decreased in cells with suppressed HRG-1, whereas transferrin receptor endocytosis is enhanced in cells that overexpress HRG-1. Cellular uptake of a fluorescent heme analogue is enhanced by HRG-1 in a V-ATPase-dependent manner. Our findings indicate that HRG-1 regulates V-ATPase activity, which is essential for endosomal acidification, heme binding, and receptor trafficking in mammalian cells. Thus, HRG-1 may facilitate tumor growth and cancer progression.
 ...
PMID:Heme-binding protein HRG-1 is induced by insulin-like growth factor I and associates with the vacuolar H+-ATPase to control endosomal pH and receptor trafficking. 1987 48

The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.
 ...
PMID:Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy. 2045 83

The normal squamous esophageal epithelium reacts as a chronic inflammation to the severe gastro-esophageal reflux. Esophagitis will progress to Barrett metaplasia in 10% of patients who would be of minor clinical interest if it then did not advance to low, high grade dysplasia and invasive carcinoma. The rise of esophageal adenocarcinoma (EAC) incidence surpasses any other cancer, including melanoma, lymphoma and small cell lung cancer. There is no clear proof that medical therapy could prevent the neoplastic progression. It seems that this population has a variable answer to proton pump inhibitors therapy. A multimodal approach of Barrett's esophagus with high grade dysplasia is required, including endoscopic mucosal resection, photodynamic therapy and thermal ablation. Photodynamic therapy could be used for the management of patients with high grade dysplasia, early EAC, local recurrence post radical therapy, microscopic involvement of tumor borders post radical resection, patient unfit / unwilling to undergo surgery. The palliation of non-resectable EAC by stenting represents the first choice. The correction of the malignant esophageal obstruction improves the symptomatology and life quality, but not survival. Because of the dismal prognosis and the frequent treatment failure of conventional treatment strategies, it seems reasonable to look for new palliative strategies.
 ...
PMID:Endoscopic therapy of Barrett's esophagus and esophageal adenocarcinoma. 2059 60

Mechanisms underlying tumor growth retarding effect of proton pump inhibitor pantoprazole (PPZ) on a murine T cell lymphoma, designated as Dalton's lymphoma (DL), were investigated. In vivo administration of PPZ to tumor-bearing mice resulted in retardation of tumor progression owing to an inhibition of tumor cell survival and augmented apoptosis. An alteration in the parameters of tumor microenvironment and modulation in the expression of cell growth regulatory molecules is indicated to be involved in PPZ-dependent tumor growth retardation. These findings will help in optimizing therapeutic strategies against cancer using PPZ.
 ...
PMID:Mechanisms of tumor growth retardation by modulation of pH regulation in the tumor-microenvironment of a murine T cell lymphoma. 2068 69


1 2 3 Next >>