EBV-Associated Gastric Cancer; An In Situ Hybridization Assay on Tissue Microarray: A Multi-Region Study from Four Major Provinces of Iran.

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran. METHODS: Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics. RESULTS: Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075). CONCLUSION: EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.

Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues.

BACKGROUND: Aerobic glycolysis rate is higher in breast cancer tissues than adjacent normal tissues which providethe ATP, lactate and anabolic precursors required for tumourgenesis and metastasis. Lactate dehydrogenase (LDH) is a critical enzyme during aerobic glycolysis as it is typically responsible for the production of lactate and regeneration of NAD(+), which allows for the continued functioning of glycolysis even in the absence of oxygen. LDH has been found to be highly expressed in breast tumors. Enzyme kinetic characteristics is related to environmentinvolving the enzyme, and tumor microenvironment has distinct features relative to adjacent normal tissues, thus we hypothesized that LDH should have different kinetic characteristics in breast tumors compared to normal breast tissues. METHODS: LDH was partially purifiedfrom human breast tumors and normal tissues, which were obtained directly from operating room. TheMichaelis-Menten constant (Km), maximum velocity (Vmax), activation energy (Ea) and enzyme efficiency in breast tumors and normal tissueswere determined. RESULTS: It was found that tumor LDH affinity in forward reaction was the same as normal LDH but Vmax of cancerous LDH was higher relative to normal LDH. In reverse reaction, affinity of tumor LDH for lactate and NAD(+) was lower than normal LDH, also enzyme efficiency for lactate and NAD(+) was higher in normal samples. The Ea of reverse reaction was higher in cancerous tissues. CONCLUSIONS: It was concluded that thelow LDH affinity for lactate and NAD(+) is a valuable tool for preserving lactate by cancer cells. We also conclude that increasing of LDH affinity may be a valid molecular target to abolish lactate dependent tumor growth and kinetic characteristics of LDH could be a novel diagnostic parameter for human breast cancer.

Prevalence of celiac disease in siblings of Iranian patients with celiac disease.

CONTEXT: Celiac disease, one of the best-known autoimmune human leukocyte antigen-dependent disorders, has a relatively increased prevalence in first-degree relatives. OBJECTIVE: To determine the prevalence of celiac disease in siblings of patients with confirmed celiac disease. METHODS: Siblings of confirmed celiac disease patients in our center were identified and enrolled in this study. Their serum immunoglobulin A and tissue transglutaminase antibody-enzyme-linked immunosorbent assay (anti-tissue transglutaminase, immunoglobulin A, and immunoglobulin G) were measured and multiple endoscopic duodenal biopsy specimens were obtained with parental consensus. Celiac disease was confirmed by observation of characteristic histological changes. RESULTS: A total of 49 children (male, 29; female, 20; age, 2-16 years) with confirmed celiac disease in a pediatric gastroenterology ward were studied from 1999 to 2006. We found 30 siblings (female, 16) all shared in both parents. The only measurement available was for immunoglobulin A tissue transglutaminase antibody. A duodenal biopsy was performed in all 30 siblings. Clinical findings such as abdominal pain, fatigue, growth retardation and diarrhea were found in 53.3% of the completely studied siblings, and positive serology without histological changes was identified in four cases. Both serology and biopsy (confirmed new cases) were positive in 2 of the 30 siblings. CONCLUSION: High prevalence of celiac disease among siblings of patients with confirmed celiac disease necessitates serologic screening (and confirmatory biopsy if indicated) in families having celiac disease. It is advantageous to diagnose the disease as soon as possible because early diagnosis and diet intervention may prevent serious complications such as growth retardation, short stature, chronic diarrhea, and malignancy.

Prevalence of celiac disease in siblings of Iranian patients with celiac disease / Prevalência de doença celíaca em filhos de pais iranianos com doença celíaca

CONTEXT: Celiac disease, one of the best-known autoimmune human leukocyte antigen-dependent disorders, has a relatively increased prevalence in first-degree relatives. OBJECTIVE: To determine the prevalence of celiac disease in siblings of patients with confirmed celiac disease. METHODS: Siblings of confirmed celiac disease patients in our center were identified and enrolled in this study. Their serum immunoglobulin A and tissue transglutaminase antibody-enzyme-linked immunosorbent assay (anti-tissue transglutaminase, immunoglobulin A, and immunoglobulin G) were measured and multiple endoscopic duodenal biopsy specimens were obtained with parental consensus. Celiac disease was confirmed by observation of characteristic histological changes. RESULTS: A total of 49 children (male, 29; female, 20; age, 2-16 years) with confirmed celiac disease in a pediatric gastroenterology ward were studied from 1999 to 2006. We found 30 siblings (female, 16) all shared in both parents. The only measurement available was for immunoglobulin A tissue transglutaminase antibody. A duodenal biopsy was performed in all 30 siblings. Clinical findings such as abdominal pain, fatigue, growth retardation and diarrhea were found in 53.3 percent of the completely studied siblings, and positive serology without histological changes was identified in four cases. Both serology and biopsy (confirmed new cases) were positive in 2 of the 30 siblings. CONCLUSION: High prevalence of celiac disease among siblings of patients with confirmed celiac disease necessitates serologic screening (and confirmatory biopsy if indicated) in families having celiac disease. It is advantageous to diagnose the disease as soon as possible because early diagnosis and diet intervention may prevent serious complications such as growth retardation, short stature, chronic diarrhea, and malignancy.

CONTEXTO: A doença celíaca, uma das mais conhecidas enfermidades autoimunes humanas, leucocitária antígeno-dependente, tem prevalência relativamente maior em parentes de primeiro grau. OBJETIVO: Determinar a prevalência de doença celíaca em irmãos de pacientes confirmadamente celíacos, filhos dos mesmos pais. MÉTODOS: Os irmãos de pacientes com doença celíaca confirmada no Department of Pediatrics, Ahvaz Jundishapur University of Medical Sciences, em Ahvaz, Iran, foram identificados e incluídos no estudo. A imunoglobulina A sérica e o anticorpo transglutaminase tecidual por ensaio imunoenzimático (anti-transglutaminase tecidual, imunoglobulina A e imunoglobulina G) foram medidos e múltiplas biopsias endoscópicas duodenais foram obtidas com o consenso dos pais. A doença celíaca foi confirmada pela observação das características histológicas. RESULTADOS: Um total de 49 crianças (29 do sexo masculino; 20 do sexo feminino; de 2 a 16 anos) com diagnóstico confirmado de doença celíaca em uma enfermaria de gastroenterologia pediátrica foi estudado de 1999 a 2006. Encontraram-se 30 irmãos (16 do sexo feminino) e todos compartilhavam os mesmos pais dos pacientes. A única medida disponível foi do anticorpo tecidual imunoglobulina A transglutaminase. A biopsia duodenal foi realizada em todos os 30 irmãos. As manifestações clínicas como dor abdominal, fadiga, retardo do crescimento e diarréia foram encontradas em 53,3 por cento dos irmãos estudados completamente, e a sorologia positiva sem alterações histológicas foi identificada em quatro casos. Ambas, sorologia e biopsia (novos casos confirmados) foram positivas em 2 dos 30 irmãos. CONCLUSÕES: A prevalência de doença celíaca entre irmãos de pais confirmadamente celíacos exige triagem sorológica e biopsia de confirmação, se indicada, em familiares com doença celíaca. Diagnosticar a doença o mais rápido possível traz vantagens, pois o diagnóstico precoce e a intervenção dietética podem prevenir complicações graves, como retardo do crescimento, baixa estatura, diarreia crônica e malignidade.