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Christos Zavos

Publications and source records attributed to Christos Zavos.

45 records · Page 3Linked to original sources

Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences.

Apoptosis is critical for organ development, tissue homeostasis, the elimination of abnormal cells and the maintenance of immune homeostasis by variable regulatory mechanisms. The death of T lymphocytes following their activation involves a series of proteases (caspases), which comprise the central executioners of apoptosis. Abnormal regulation of apoptosis results in disease. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of the chronic inflammatory process in inflammatory bowel disease with potential tumourigenic effect. The use of antitumour necrosis factor-alpha, anti-interleukin-6R and anti-interleukin-12 antibodies suppresses colitis activity by induction of T-cell apoptosis, thereby having important implications for the design of effective therapeutic strategies in inflammatory bowel diseases. Contrary to international data, the incidence of cancer in Greek patients with inflammatory bowel disease appears to be low. A balance between cell proliferation (Ki-67 overexpression) and apoptosis (Bax protein overexpression) may partly explain the low incidence of cancer development in Greek inflammatory bowel disease patients.

Animals↗

Eradication of Helicobacter pylori may be beneficial in the management of chronic open-angle glaucoma.

BACKGROUND: We have documented a high prevalence of Helicobacter pylori infection in patients with glaucoma. OBJECTIVE: To evaluate the effect of H pylori eradication on the 2 most commonly used glaucoma parameters: intraocular pressure and visual field. METHODS: A total of 41 patients with glaucoma and 30 age-matched anemic controls underwent upper gastrointestinal endoscopies and gastric mucosal biopsies to detect the presence of H. pylori infection by histologic analysis and rapid urease test (CLOtest; Delta West, Draper, Utah). Saliva samples were also tested by CLOtest. Serum anti-H pylori-specific IgG was analyzed by enzyme-linked immunosorbent assay. Helicobacter pylori-positive patients received a triple eradication regimen (omeprazole, clarithromycin, and amoxicillin treatment), and all patients were observed for 2 years while remaining under the same antiglaucoma therapy. RESULTS: Helicobacter pylori was detected in 88% of glaucoma cases and in 47% of controls (P<.001). Helicobacter pylori eradication was successful in 83% of treated patients. At the 2-year clinical end point, glaucoma parameters (mean intraocular pressure and mean visual field parameters) were improved in the subgroup of patients where H. pylori eradication was successful (P<.001 for intraocular pressure; P< or =.01 for visual field parameters), but not in the other patients. CONCLUSION: Helicobacter pylori eradication may positively influence glaucoma parameters, suggesting a possible causal link between H pylori and glaucoma.

Aged↗

Immunomodulatory benefits of cyclosporine A in inflammatory bowel disease.

Etiopathogenesis of mucosal inflammation in inflammatory bowel disease remains a complex and enigmatic field; various factors (genetic, environmental and microbial) trigger an event that activates intestinal immune and nonimmune systems culminating in inflammation and tissue injury. Specifically, both innate and adaptive immune systems seem to play important roles in the pathophysiology of this disease. Cyclosporine A represents a macrolide immune modulator with primary inhibitory effects on T helper lymphocyte production of interleukin-2, and other cytokines leading to altered T-lymphocyte and B-lymphocyte function. The diversity of its therapeutic outcome reported in inflammatory bowel disease may be due to the intricate immuno-pathogenic profile of the disease and the variety of the applied dose-dependent courses of therapy. Cyclosporine A exerts additional actions on other components of the inflammatory infiltrate, including neutrophils and mast cells, thereby appearing to be a multi-dynamic therapeutic approach, although with potential drawbacks, that may be applied alone or combined with other immunomodulatory agents in inflammatory bowel disease patients. Because cyclosporine A induces apoptosis of T-lymphocytes responsible for perpetuation of the chronic inflammatory process in the disease with potential tumorigenic effect, it may exert a further inhibitory effect on cancer development in inflammatory bowel disease patients, and can be combined with other relative agents, such as rapamycin, which also promotes T-lymphocyte apoptosis. Therefore, recently established multifactorial action of cyclosporine A in relation to the pathogenesis of the disease can open new horizons for prospective, controlled trials in large cohorts, aiming to emphasize cyclosporine A's potential.

Colitis, Ulcerative↗

Apoptosis in hepatocellular carcinoma.

The process of apoptosis plays a crucial role in several physiological as well as pathophysiological processes, and is a fundamental mechanism for the deletion of unwanted, senescent, or damaged cells. Defects in the apoptotic mechanisms or, even more, disturbances of the equilibrium between cellular replication, growth, differentiation and apoptosis favor the growth of preneoplastic and tumoral lesions in the liver. Clinical and molecular medical analyses have yielded a considerable amount of information about liver oncogenesis. Studies on transgenic models of hepatocarcinogenesis have allowed a meticulous examination of the roles of apoptosis, tumor suppressors, DNA repair processes and other events in the clonal expansion and accumulation of genetic lesions. During initiation, there is rapid proliferation and a high amount of apoptosis, whereas in the promotion stage, there is decreased cell death and increased cell proliferation. Accumulating evidence suggests a defective apoptotic process in human hepatocellular carcinoma. Moreover, a range of prognostic factors related to apoptosis might be used in the early assessment of the progress of hepatocarcinogenesis as well as in hepatocellular carcinoma recurrence. Lastly, many potential therapeutic strategies, that induce the apoptotic process in various ways, can be applied to the hepatocellular carcinoma management.

Apoptosis↗

Locoregional immunochemotherapy in primary and metastatic liver disease: meta-analysis and review of literature.

BACKGROUND/AIMS: Primary and metastatic liver tumors are the most common malignancies that resist conventional chemotherapy and radiotherapy. Several immunotherapies have been attempted for cancer treatment on the basis of stimulating host immune response to tumors and recent development of combined targeting locoregional immunochemotherapy reported with promising results. However, the efficacy of this therapeutic modality is not yet widely established. METHODOLOGY: We reviewed the medical literature for publications dealing with the value of locoregional immunochemotherapy in patients with primary or metastatic liver tumors. RESULTS: We found that 5 and 7 studies have been controlled and inadequately controlled, respectively. Among 131 patients with primary liver cancer, 40 were treated with combined locoregional immunochemotherapy, and 20 with systemic immunochemotherapy, and 71 with systemic chemotherapy served as two control groups. Complete or partial response was observed in 32 out of 40 (80%) patients who received combined locoregional therapy, and in 10 out of 20 (50%) systemic immunochemotherapy controls (P = 0.03). Survival was three times higher in the patients who received combined locoregional therapy compared with systemic chemotherapy controls (18 vs. 5.6 months). Recurrence of tumor was higher in systemic immunochemotherapy controls (P = 0.003). Among 286 patients with metastatic liver disease, 180 patients were treated with combined locoregional immunochemotherapy and 106 patients with systemic immunochemotherapy. Response (complete or partial) was observed in 65 out of 98 (66.3%) patients who received combined therapy, and in 4 out of 26 (15.4%) controls (P < = 0.001). Survival was two-fold higher in the patients treated with combined therapy (21 vs. 10.5 months). Tumor recurrence was higher in the systemic immunochemotherapy controls (P < = 0.001). CONCLUSIONS: The observational studies indicate a plausible therapeutic rationale for the introduction of locoregional immunotherapy in patients with primary and metastatic liver disease.

Chemotherapy, Adjuvant↗

New concepts of molecular biology on gastric carcinogenesis.

Gastric cancer not located in the cardia still remains the second most common cancer worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric cancer can be subdivided into two distinct pathologic entities, diffuse and intestinal, that have different epidemiologic and prognostic features. Various genetic and environmental factors play important roles in gastric carcinogenesis; both lead to either abnormal genes overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in the genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon cancer pathogenesis, whereas it remains tentative whether the diffuse type of malignancy follows an analogous progression. The most common genetic abnormalities in gastric cancer tend to be loss of heterozygosity of tumor suppressor genes, particularly of p53 or "Adenomatous Polyposis Coli" gene. The latter leads to gastric oncogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to neoplasia. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to gastric cancer of the diffuse type. Amplification and/or overexpression of putative trophic factors have also been observed in gastric cancer. Finally, Helicobacter pylori (H. pylori) infection is also involved in gastric carcinogenesis through various mechanisms, thereby necessitating H. pylori eradication in patients with gastric cancer.

Cell Transformation, Neoplastic↗

The role of endoscopic treatment in postoperative bile leaks.

BACKGROUND/AIMS: Bile leak is among the most common and serious complications of biliary tract surgery. The aim of this non-randomized study was to evaluate the role of endoscopic intervention as an accepted treatment for this complication. METHODOLOGY: An endoscopic retrograde cholangiopancreatography (ERCP) database was reviewed retrospectively to identify all cases of bile leak related to cholecystectomy (laparoscopic or open). Patients' records and endoscopy reports were reviewed. Moreover, structured telephone interviews were conducted to collect data. RESULTS: Twenty-four patients, 4 males and 20 females, with a median age of 54 (range 28-76 years) with suspected postcholecystectomy bile leaks were referred for ERCP performed 3-73 days after operation (mean 9.5 days). All but one case had high-grade bile-like liquid outflowing from the original drainage tubes or the fistulous tract of T-tube. One patient presented with bilious ascites, 17 patients had sudden or gradual abdominal pain, 3 jaundice, 2 abdominal pain with fever, and 1 nausea and vomiting. ERCP was successful in all cases, and revealed leakage from the cystic stump in 10 cases, from a common bile duct (CBD) defect in 6, from a common hepatic duct defect in 3, from the gallbladder bed in 2, from a T-tube track in 1, and complete CBD transection in 2 patients. Seventeen patients were successfully treated by endoscopic sphincterotomy (ES) plus endoprosthesis, 3 by stent placement without sphincterotomy, 2 with complete transection by proximal hepaticojejunostomy, and 2 patients with leakage from the cystic stump and a CBD defect were operated after unsuccessful endoscopic intervention. CONCLUSIONS: ERCP is recommended as a safe and efficacious intervention to detect and treat postoperative bile leaks. ES plus endoprosthesis is effective for the treatment of bile leakage. Endoscopic stenting without sphincterotomy may be offered as a primary option in young patients with postoperative bile leaks.

Adult↗