Duodenal carcinoma at the ligament of Treitz. A molecular and clinical perspective.

BACKGROUND: There is very small occurrence of adenocarcinoma in the small bowel. We present a case of primary duodenal adenocarcinoma and discuss the findings of the case diagnostic modalities, current knowledge on the molecular biology behind small bowel neoplasms and treatment options. CASE: The patient had a history of iron deficiency anemia and occult bleeding with extensive workup consisting of upper endoscopy, colonoscopy, capsule endoscopy, upper gastrointestinal series with small bowel follow through and push enteroscopy. Due to persistent abdominal pain and iron deficiency anemia the patient underwent push enteroscopy which revealed adenocarcinoma of the duodenum. The patient underwent en-bloc duodenectomy which revealed T3N1M0 adenocarcinoma of the 4th portion of the duodenum. CONCLUSIONS: Primary duodenal carcinoma, although rare should be considered in the differential diagnosis of occult gastrointestinal bleeding when evaluation of the lower and upper GI tract is unremarkable. We discuss the current evaluation and management of this small bowel neoplasm.

The role of epigenetics in environmental and occupational carcinogenesis.

Over the last few years there has been an increasing effort in identifying environmental and occupational carcinogenic agents and linking them to the incidence of a variety of human cancers. The carcinogenic process itself is multistage and rather complex involving several different mechanisms by which various carcinogenic agents exert their effect. Amongst them are epigenetic mechanisms often involving silencing of tumor suppressor genes and/or activation of proto-oncogenes, respectively. These alterations in gene expression are considered critical during carcinogenesis and have been observed in many environmental- and occupational-induced human cancers. Some of the underlying mechanisms proposed to account for such differential gene expression include alterations in DNA methylation and/or histone modifications. Throughout this article, we aim to provide a current account of our understanding on how the epigenetic pathway is involved in contributing to an altered gene expression profile during human carcinogenesis that ultimately will allow us for better cancer diagnostics and therapeutic strategies.

The role of reactive oxygen species and oxidative stress in environmental carcinogenesis and biomarker development.

Although we have greatly benefited from the use of traditional epidemiological approaches in linking environmental exposure to human disease, we are still lacking knowledge in to how such exposure participates in disease development. However, molecular epidemiological studies have provided us with evidence linking oxidative stress with the pathogenesis of human disease and in particular carcinogenesis. To this end, oxidative stress-based biomarkers have proved to be essential in revealing how oxidative stress may be mediating toxicity induced by many known carcinogenic environmental agents. Therefore, throughout this review article, we aim to address the current state of oxidative stress-based biomarker development with major emphasis pertaining to biomarkers of DNA, lipid and protein oxidation.

Viral-induced human carcinogenesis: an oxidative stress perspective.

Oncogenic transformation occurs via many different mechanisms. Alterations in the expression of certain key genes (oncogenes and/or tumor suppressor genes) contribute to the development of the tumorigenic state of uncontrolled cell proliferation. Tumor viruses' studies have contributed over the last 2 decades significantly in cancer etiology, first by providing valuable information on the mechanisms and dissection of cell signaling and growth control pathways and second by being causative agents of human neoplasia. Viruses contribute to the development of the neoplastic state through many mechanisms: inactivation of tumor suppressor genes, hyperstimulation of cellular proto-oncogene transcription, or by viral protein interference with the cellular transcription, signal transduction, DNA repair and apoptosis pathways and induction of chronic oxidative stress. On the other hand, only recently research has provided evidence of the epigenetic pathway involvement and especially the DNA methylation machinery. To this end, both hypomethylation-induced oncogenic activation and/or hypermethylation-induced tumor suppressor gene silencing are linked with viral-induced carcinogenesis. In this review, we discuss the current status of knowledge on viral-associated carcinogenesis with emphasis on the mechanisms of oxidative stress and DNA damage induction in humans by viruses as well as implications in cancer treatment.

BRCA1 involvement in toxicological responses and human cancer etiology.

Breast cancer associated gene 1 (BRCA1) gene is located on the long (q) arm of chromosome 17 at position 21. In the nucleus of many types of normal cells, BRCA1 protein interacts with several other proteins to mend strand breaks in DNA. It is generally considered a key regulatory protein participating in cell cycle checkpoint and DNA damage repair networks. Exposure to various environmental and genetic factors can induce a severe impact on life span and lead to neoplastic transformation. BRCA1 through its participation in the control mechanisms of cell growth and DNA repair is lately considered as an important component of mammary homeostasis. In this review we summarize the different cellular functions and roles of this gene, the experimental evidence for its linkage to carcinogenesis and recent evidence tying BRCA1 to environmentally induced toxic-stress responses. Finally, we discuss the new insights in the exploitation of BRCA1 defects for the development of new therapeutic strategies in cancer treatment and clinical applications.