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Gastrointestinal Cancers (gastrointestinal + cancers)

Distribution by Scientific Domains

Medical Sciences	90%

Selected Abstracts

INSULIN-LIKE GROWTH FACTOR-I RECEPTOR AS A CANDIDATE FOR A NOVEL MOLECULAR TARGET IN GASTROINTESTINAL CANCERS

DIGESTIVE ENDOSCOPY, Issue 4 2006
Yasushi Adachi
Abnormal activation of growth factor receptors and their signal pathways are required for neoplastic transformation and tumor progression. The concept of targeting specific tumorigenic receptors has been validated by successful clinical application of multiple new drugs, such as those acting against HER2/neu, epidermal growth factor receptor 1, and c-Kit. In this review, we focus on the next promising therapeutic molecular target of insulin-like growth factor (IGF)-I receptor (IGF-Ir). The IGF/IGF-Ir system is an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity in a number of neoplastic diseases, including human gastrointestinal carcinomas. Preclinical studies demonstrated that downregulation of IGF-Ir signals reversed the neoplastic phenotype and sensitized cells to antitumor treatments. We summarize a variety of ways to disrupt IGF-Ir function. Then, we introduce our strategy of adenoviruses expressing dominant negative of IGF-Ir (IGF-Ir/dn) against gastrointestinal cancers, including stomach, colon, and pancreas. IGF-Ir/dn suppresses tumorigenicity both in vitro and in vivo and increases stressor-induced apoptosis. IGF-Ir/dn expression upregulates chemotherapy-induced apoptosis and these combination therapies with chemotherapy are very effective against tumors in mice. Some drugs blocking IGF-Ir function are now entering clinical trial, thus IGF-Ir might be a candidate for a therapeutic target in several gastrointestinal malignancies. [source]

Helicobacter pylori Infection may be Implicated in the Topography and Geographic Variation of Upper Gastrointestinal Cancers in the Taihang Mountain High-Risk Region in Northern China

HELICOBACTER, Issue 5 2010
Denggui Wen
Abstract Backgrounds:,Helicobacter pylori infection is prevalent in China. Chronic infection of the bacterial not only causes distal stomach cancer, but also confers risk to gastric cardia adenocarcinoma. Because H. pylori infection is inversely associated with esophageal adenocarcinoma, globally the infection rate is significantly correlated with the ratio of squamous carcinoma to adenocarcinoma of the esophagus. These agree with the topography of upper gastrointestinal cancer observed in the Taihang Mountain high-risk region where both gastric cardia and non-cardia adenocarcinoma coincide with esophageal squamous cancer, but with almost no distal esophageal adenocarcinoma. Moreover, as altitude increases from plain to mountains, we observed progressively increasing incidence rates of gastric adenocarcinomas in recent years in the region. Because H. pylori infection is a definite carcinogen to gastric adenocarcinoma and is more prevalent in the mountain than in plain areas due to undeveloped living conditions, the observation gives the impression as though H. pylori infection is implicated. Aims:, This article aims to note the role of H. pylori infection in upper gastrointestinal cancer in the Taihang Mountain high-risk region in northern China. Materials and Methods:, First the unique topography and geographic variation of upper gastrointestinal cancer in the region is described to indicate a possible role of H. pylori infection, then we review studies on prevalence of H. pylori infection in the high-risk region and describe difference in socioeconomic development and water hygiene between the plains and the mountains as related to the prevalence of H. pylori infection. Results:, Coincidence of gastric cancer in the region and a progressively increasing rate of the cancer from the plain towards the mountains indicate H. pylori infection may be implicated in upper gastrointestinal cancer. Conclusion:, International collaboration is needed to study H. pylori and upper gastrointestinal cancer in the region when rapid industrialization is just beginning. [source]

INSULIN-LIKE GROWTH FACTOR-I RECEPTOR AS A CANDIDATE FOR A NOVEL MOLECULAR TARGET IN GASTROINTESTINAL CANCERS

Changing trends in gastrointestinal disease in the Asia,Pacific region

JOURNAL OF DIGESTIVE DISEASES, Issue 4 2007
KL GOH
The new millennium has seen distinct changes in the pattern of gastrointestinal disease in the Asia,Pacific region. These changes are important as more than half of the world's population come from the region and therefore impact significantly on the global disease burden. The highest incidence of gastric cancer (GCA) has been reported from Asia and GCA remains a very important cancer. However time-trend studies have shown a decrease in GCA incidence in several countries in Asia. A rise in cardio-esophageal cancers as seen in the West has not been reported. On the other hand, colorectal cancer has been steadily increasing in Asia with age-standardized incidence rates of some countries approaching that of the West. The pattern of acid-related diseases has also changed. Gastroesophageal reflux disease is a fast emerging disease with an increasing prevalence of reflux esophagitis and reflux symptoms. The prevalence of peptic ulcer disease has at the same time declined in step with a decrease in H. pylori infection. Many of the changes taking place mirror the Western experience of several decades ago. Astute observation of the epidemiology of emerging diseases combined with good scientific work will allow a clearer understanding of the key processes underlying these changes. With rapid modernization, lifestyle changes have been blamed for an increase in several diseases including gastroesophageal reflux disease, nonalcoholic fatty liver disease and colorectal cancer. A worrying trend has been the increase in obesity among Asians, which has been associated with an increase in metabolic diseases and various gastrointestinal cancers. Conversely, an improvement in living conditions has been closely linked to the decrease in GCA and H. pylori prevalence. [source]

Chemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis induced by N-methyl-N,-nitro-N-nitrosoguanidine in rats

JOURNAL OF DIGESTIVE DISEASES, Issue 3 2006
Su Juan FEI
OBJECTIVES: Epidemiological and experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) are chemopreventive agents of gastrointestinal cancers, but few studies on gastric cancer have been carried out. A decrease in folic acid supplement and subsequent DNA hypomethylation are related to gastrointestinal cancers, and it has been shown that high-dose folic acid may interfere with gastric carcinogenesis in dogs. The objective of this study was to investigate the effects of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and folic acid on the chemoprevention of gastric cancer induced by N-methyl-N,-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, and to evaluate the cell proliferation of gastric mucosa in different experimental groups. METHODS: Eighty male Wistar rats were randomly divided into five groups (16 rats in each group). In the control group, the rats were given pure water and basal diet. In the MNNG group, the rats received MNNG in drinking water (100 mg/L) and basal diet. In the MNNG + low-dose rofecoxib group, the rats were given MNNG and rofecoxib 5 mg/kg per day with basal diet. In the MNNG + high-dose rofecoxib group, the rats were given MNNG and rofecoxib 15 mg/kg per day with basal diet. In the MNNG + folic acid group, the rats were given MNNG and folic acid 5 mg/kg per day with basal diet. The experiment was terminated at 50 weeks, and all rats were killed. Blood samples of 3 mL were obtained for measurement of serum folic acid concentrations in the control group, the MNNG group and the MNNG + folic acid group by using chemiluminescent method. The stomach was removed from all rats for histopathological examination and immunohistochemical study. Proliferating cell nuclear antigen (PCNA) expression in gastric epithelial cells was also determined. RESULTS: In the MNNG group, five of 11 rats (45.5%) developed gastric cancer, while in all other four groups no gastric cancer was found (P < 0.05). The positivity rate of PCNA expression in the cancerous tissues was significantly higher than that in the non-cancerous tissues (80.0%vs 14.1%, P < 0.05). The positivity rate of PCNA expression in the gastric mucosal cells of the MNNG group was significantly higher than that in the other four groups. The mean serum folic acid concentration of rats was significantly higher in the MNNG + folic acid group (193.70 ± 60.73 ng/mL) than those in the control group (84.21 ± 25.26 ng/mL) and the MNNG group (72.27 ± 16.70 ng/mL, P < 0.05). It was shown that both low- and high-dose rofecoxib as well as folic acid interfered with the development of gastric cancer induced by MNNG in Wistar rats. CONCLUSIONS: The results indicate that rofecoxib as well as folic acid interferes with gastric carcinogenesis induced by MNNG in Wistar rats, and the suppression of gastric cell proliferation may play a crucial role in the chemoprevention of gastric cancer by rofecoxib and folic acid. The higher serum folic acid concentration of rats may play an important role in the prevention of gastric cancer. [source]

MicroRNAs: Master Regulators of Ethanol Abuse and Toxicity?

ALCOHOLISM, Issue 4 2010
Rajesh C. Miranda
Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects leading to the suggestion that ethanol is a "dirty drug." An important question is, are there cellular "master-switches" that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol-sensitive miRNAs are indeed regulatory master-switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol-sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol's effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol-related disorders. [source]

Meta-analysis: the use of non-steroidal anti-inflammatory drugs and pancreatic cancer risk for different exposure categories

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2007
G. CAPURSO
Summary Background, A better understanding of predictors of risk for pancreatic ductal adenocarcinoma (PDAC) could inform preventive efforts against this lethal cancer. While aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDS) might protect against several gastrointestinal cancers, their role in the development of PDAC remains unclear. Aim, To conduct a systematic review and meta-analysis on the relation between ASA/NSAIDs exposure and the risk of PDAC. Methods, We searched Pubmed, Embase, Scopus, Cochrane database of systematic reviews and reference lists of identified papers and included observational (cohort or case-control) studies and randomized controlled trials examining exposure to ASA and/or NSAIDs and the incidence or mortality of PDAC. We defined three categories (low, intermediate, high), based on exposure duration and dose. Results, Eight studies fulfilled our inclusion criteria (four cohort, three case controls, and one randomized controlled trial studies) enrolling 6301 patients between 1971,2004; all but one study took place in the US. The pooled OR were 0.99 (0.83,1.19), 1.11 (0.84,1.47) and 1.09 (0.67,1.75) in the low, intermediate and high exposure groups respectively, with considerable heterogeneity (I2 ranging 60,86%). Sensitivity analysis by ASA use only, study design or sex did not reveal additional important information. Conclusions, This study did not show an association between ASA/NSAIDs and PDAC. The large baseline exposure in controls in North-America may have obscured an association. There is need for additional studies, especially in Europe, to clarify this issue. [source]

The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2004
A. Kerber
Summary Background :,Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. Aim :,To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. Methods :,We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. Results :,Receiver,operator curve analysis revealed <0.7 ,g/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). Conclusion :,The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice. [source]

Immunohistochemical study of cyclooxygenase-2 and p53 expression in skin tumors

THE JOURNAL OF DERMATOLOGY, Issue 5 2006
Kwang Ho KIM
ABSTRACT Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various cancers, including experimentally promoted tumors, gastrointestinal cancers, breast tumors and skin tumors. The mechanism that controls COX-2 expression is not yet clear. Currently, it is reported that COX-2 expression is frequently associated with mutated p53 genes. The goal of this study was to evaluate the expression patterns of COX-2 and p53 in several skin tumors and their correlation. An immunohistochemical method was used to investigate the expression of COX-2 and p53 proteins on formalin-fixed, paraffin-embedded tissue specimens of squamous cell carcinomas (SCC), basal cell carcinomas (BCC), Bowen's disease (BD), actinic keratosis (AK) and porokeratosis. The expression of COX-2 increased in 50% (5/10) of SCC, 80% (8/10) of BCC, 40% (4/10) of BD, 50% (5/10) of AK, and 20% (2/10) of porokeratosis cases. The expression of p53 increased in 90% (9/10) of SCC, 70% (7/10) of BCC, 70% (7/10) of BD, 50% (5/10) of AK, and 40% (4/10) of porokeratosis cases. COX-2 positivity rates of the p53-positive skin tumors were 56%, 100%, 57%, 80% and 25% in SCC, BCC, BD, AK and porokeratosis, respectively. However, the correlation between p53 and COX-2 expression in skin tumors was not statistically significant (P > 0.05). Our results indicate that skin COX-2 and p53 may play roles in skin tumors, but that there is no apparent correlation between the two markers. [source]

Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site

CANCER, Issue 10 2010
A phase 2 trial of the Sarah Cannon Oncology Research Consortium
Abstract BACKGROUND: Despite the widespread use of oxaliplatin-based regimens for colorectal and other gastrointestinal cancers, there is surprisingly little information regarding their empiric use for the treatment of carcinoma of unknown primary site (CUP). In the current study, the combination of oxaliplatin and capecitabine in patients with recurrent and refractory CUP was examined. METHODS: Patients with CUP who had received at least 1 previous chemotherapy regimen were treated with oxaliplatin (130 mg/m2 intravenously on Day 1) and capecitabine (1000 mg/m2 orally twice daily on Days 1-14). Treatment cycles were repeated every 21 days. Patients with objective response or stable disease after 2 cycles continued treatment for 6 cycles or until disease progression. RESULTS: Nine of 48 patients (19%) had objective responses to treatment; an additional 22 patients had stable disease at the time of first re,evaluation. After a median follow-up of 17 months, the median progression-free and overall survivals were 3.7 months and 9.7 months, respectively. This regimen was reasonably well tolerated by most patients. CONCLUSIONS: The combination of oxaliplatin and capecitabine was found to have activity as a salvage treatment for patients with CUP. This regimen should be considered in patients with clinical and pathologic features suggesting a primary site in the gastrointestinal tract. Further development of the regimen as a first-line therapy, or with bevacizumab added, is indicated. Cancer 2010. © 2010 American Cancer Society. [source]

Constitutive deficiency in DNA mismatch repair

CLINICAL GENETICS, Issue 6 2007
KEA Felton
Mutations in the DNA mismatch repair (MMR) genes are associated with the inheritance of hereditary non-polyposis colorectal cancer, also known as Lynch syndrome, a cancer syndrome with an average age at onset of 44. Individuals presenting with colorectal cancer are diagnosed with Lynch I, whereas individuals who present with extra-colonic tumors (such as endometrial, stomach, etc.) are identified as patients with Lynch syndrome II. Recently, 30 families have been reported with inheritance of biallelic mutations in the MMR genes. Here we summarize the phenotype of individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein or greatly compromised protein function. In contrast to individuals with Lynch syndrome I and II, individuals with no MMR function present with childhood onset of hematological and brain malignancies, whereas residual MMR function can also result in gastrointestinal cancers and an age of onset in the second to fourth decade. Individuals with biallelic MMR mutations often present with café-au-lait spots, regardless of the level of MMR function remaining. Thus, the inheritance of two MMR gene mutations is a separate entity from Lynch I or II or the subtypes Turcot and Muir,Torre. [source]