1,721,005 research outputs found
IMMUNOHISTOCHEMICAL EVIDENCE OF P53 OVEREXPRESSION IN GASTRIC EPITHELIAL DYSPLASIA
Molecular abnormalities of the p53 gene in chromosome 17p may be among the most commonly observed in human cancer. Their role in gastric carcinogenesis is suggested by their frequent detection in invasive adenocarcinomas. To investigate the chronology with which these abnormalities appear in the gastric carcinogenesis process, the expression of p53 proteins was investigated in late stages of the process, namely dysplasia, and in superficial carcinomas. A polyclonal antibody, CM-1, against both wild-type and mutant proteins was applied to paraffin-embedded biopsy and gastrectomy specimens previously fixed in buffered formalin. Positive nuclear stain was obtained in 36.4% of 33 cases of gastric epithelial dysplasia, corresponding to 19% of mild, 27.3% of moderate, and 64.3% of severe dysplasias. Eight of 13 (61.5%) invasive carcinomas showed positive stain. The data indicate an increased incidence of p53 abnormalities in the late stages of gastric carcinogenesis
MicroRNA Dysregulation in Esophageal Neoplasia: The Biological Rationale for Novel Therapeutic Options.
While the phenotypic changes involved in the esophageal oncogenic cascade are now well established, the molecular profiling of this pathway remains unreliable. Our understanding of the molecular dysregulations underlying the development/progression of cancer has recently been expanded by the characterization of a new class of small, noncoding RNA gene products, the microRNAs (or miRNAs). These endogenous silencers target a large number of genes, functioning as tumor suppressors or tumor promoters, depending on the activity of the targeted genes. In esophageal cancer, miRNA dysregulation plays a significant part in the molecular oncogenic pathway, in cancer prognosis, and in patients responsiveness to neo-adjuvant and adjuvant therapies. In addition to these valuable features, miRNAs have been proposed as innovative therapeutics per se and as plausible biological targets in new treatment strategies
Role of miRNA in distinguishing primary brain tumors from secondary tumors metastatic to the brain.
Cancer is the result of complex processes that involve multiple molecular alterations. The understanding of such complexity has been improved by the advent of a new class of small, noncoding RNA gene products known as microRNAs (or miRNAs). miRNAs play an essential role in cancer development and progression by modulating gene expression binding to target mRNA, causing either mRNA degradation or translation inhibition. Several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic and prognostic implications. Beyond these valuable features, miRNAs could be potentially used in the future as innovative and targeted therapeutics. Recent in vitro and expression profiling studies have identified that specific miRNAs are directly involved in brain carcinogenesis and in the metastatic process. This review focuses on metastasis-related miRNAs and on the role of miRNAs in distinguishing between primary and metastatic brain tumors. In clinical practice, miRNAs could represent a promising new class of cancer biomarkers in the diagnosis and management of brain neoplastic lesions
Targeted therapies in the management of metastatic bladder cancer.
The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of molecular pathways upon which new therapeutic approaches can be targeted. New agents and strategies have recently been developed which can direct the most appropriate choice of treatment for advanced disease. A review of literature published on the targeted therapy for metastatic bladder cancer is presented, focusing on the molecular pathways shut down by the new therapeutic agents
GASTRIC EPITHELIAL DYSPLASIA - A PROSPECTIVE MULTICENTER FOLLOW-UP-STUDY FROM THE INTERDISCIPLINARY-GROUP-ON-GASTRIC- EPITHELIAL-DYSPLASIA
To assess the evolution of gastric epithelial dysplasia (GED), a prospective multicenter study was based on a protocol of repeated endoscopies and biopsies. To date, 134 cases (0.4% of all patients endoscopically examined in the same period) have been diagnosed as having GED and 80 of those have had an "adequate" follow-up (at least three endoscopies). Mean follow-up time was 18 months. Gastric epithelial dysplasia was mild in 59% of cases, moderate in 25%, and severe in 10%. Six percent of the patients had lesions that were "indefinite for dysplasia." Chronic atrophic gastritis (40%), gastric ulcer (32%), gastrectomy (10%), and polyps (9%) were the most frequently associated lesions. The term "regression" was adopted for GED no longer detectable during follow-up and the term "progression" was used when more severe changes or cancer was detected. Mild GED regressed in 66% of cases, persisted in 15%, and progressed in 19% (three cases to moderate, one to severe, and five to cancer). Moderate GED regressed in 30% of patients, persisted in 30%, and progressed in 40% (one to severe GED and seven to cancer). Severe GED regressed in 12.5% of patients, persisted in 12.5%, and progressed to cancer in 75%. Of the five patients with lesions indefinite for dysplasia, two had no dysplastic changes at follow-up and three had cancer diagnosed. Ten of 21 cases of cancer (48%) were at the early stage. The diagnosis was reached within the first year of follow-up in 14 cases and after 1 year in seven (13 to 39 months). Fifteen of 21 cases of cancer were diagnosed in gastric ulcer patients. In conclusion, GED is an infrequent finding and its biologically neoplastic significance is confirmed by the results of the follow-up study: (1) in its mild form, it tends to regress but adequate subsequent check-ups are mandatory as it may associate with or evolve as cancer; (2) patients with moderate GED require strict follow-up since the lesion shows a higher cancer risk; (3) surgery is indicated for severe GED because gastric cancer develops in 75% of cases; and (4) patients with lesions indefinite for dysplasia should immediately undergo repeat endoscopy and biopsy. Such an approach allows gastric cancer to be detected at an early stage in a much higher percentage of cases than may be expected.
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