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Nadir Arber

Publications and source records attributed to Nadir Arber.

At least 37 records · Page 2Linked to original sources
PubMed2005

Inflammation-related erythrocyte aggregation in patients with inflammatory bowel disease.

Chronic inflammation is associated with increased erythrocyte adhesiveness/aggregation. This might have deleterious effects on the microcirculatory flow and tissue oxygenation. We aimed to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with inflammatory bowel disease (IBD). Fifty-two patients (24 women and 28 men) with ulcerative colitis (UC) at a mean age of 44.0+/-16.8 years and 96 patients (44 women and 52 men) with Crohn's disease (CD) at a mean age of 38.0+/-15.5 years, with various degrees of disease activity, were matched to normal controls. A simple slide test and image analysis were used to determine the degree of erythrocyte adhesiveness/aggregation. CD activity index (CDAI) was determined in patients with CD, while clinical colitis activity index was applied for patients with UC. A significant (P < 0.0005) increment in the degree of erythrocyte adhesiveness/aggregation was noted in both groups of IBD patients compared with matched control groups. This increment was evident even in individuals with a low index of disease activity and during remission. The highly significant correlation with the concentrations of fibrinogen suggests that the degree of erythrocyte adhesiveness/aggregation is an inflammation-related phenomenon. An enhanced state of erythrocyte adhesiveness/aggregation was noted in the peripheral blood of patients with IBD. This might have a deleterious effect on intestinal microcirculatory flow and tissue oxygenation.

Adult↗
PubMed2005

Emerging technologies in colorectal cancer screening.

CRC is a preventable disease through early detection, yet screening rates remain low and mortality rates remain high. The discomfort associated with the preparation and performance of some of the currently available screening modalities and the lack of public awareness about CRC and screening procedures likely account for low rates of screening. CT colonography and stool DNA testing are new promising screening technologies that are less invasive, accurate, and suitable for the public more than the current screening procedures. Before both tests can be promoted for population-based screening programs, several issues that have been detailed in this article must be addressed further, including technical improvements for improving accuracy, development of virtual preparation, test availability, patient and provider acceptability and cost-effectiveness for CTC, and identifying the optimal combination of molecular targets for stool DNA testing. The year 2005 will tell us if the ideal technology from the public health point of view was achieved. A skill-independent, anesthesia-free, self-propelling, self-navigating miniaturized endoscopic device that may move along the entire length of the colon may change the natural history of CRC. We should aim to achieve a new definition of CRC--a rare disease occurring in a subset of the population who has not been screened for the disease.

Colonoscopy↗
PubMed2005

Initial experience of videocapsule endoscopy for diagnosing small-bowel tumors in patients with GI polyposis syndromes.

BACKGROUND: Small-bowel tumors frequently occur in familial adenomatous polyposis and other GI polyposis syndromes. These tumors are difficult to detect with conventional techniques. Our aim was to assess the utility of videocapsule endoscopy in the detection of small-bowel tumors in this setting. METHODS: We examined 19 familial adenomatous polyposis patients and 3 patients with either Peutz-Jeghers syndrome, hyperplastic polyposis, or Cowden disease. OBSERVATIONS: Prevalence of small-bowel polyps on videocapsule endoscopy was 59% in all patients, 52.6% in familial adenomatous polyposis patients, and 75% in a subgroup of familial adenomatous polyposis patients with exon 15 mutations. Videocapsule endoscopy was safe and well tolerated in all patients. CONCLUSIONS: Videocapsule endoscopy has a high yield in detecting small-bowel tumors in patients with GI polyposis syndromes. It may be especially indicated in familial adenomatous polyposis patients with the aggressive phenotype of the disease, e.g., mutations in exon 15.

Adenomatous Polyposis Coli↗
PubMed2005

Chemoprevention of colorectal cancer: ready for routine use?

In the third millennium preventive medicine is becoming a corner stone in our concept of health. Colorectal cancer (CRC) prevention, in particular, has become an important goal for health providers, physicians and the general public. CRC fits the criteria of a disease suitable for chemopreventive interventions. It is a prevalent disease that is associated with considerable mortality and morbidity rates, with more than 1,000,000 new cases and 500,000 deaths expected, worldwide, in 2004. CRC has a natural history of transition from precursor to malignant lesion that spans, on average, 15-20 years, providing a window of opportunity for effective interventions and prevention. A pre-malignant precursor lesion (i.e., adenoma) usually precedes cancer, and helps to identify a subset of the population that is at increased risk of harbouring and developing cancer. Science and technology have evolved to a point where we are able to use our knowledge of cancer biology to identify individuals at risk and interrupt the process of malignant transformation at the level of the pre-cancerous lesion. Recent progress in molecular biology and pharmacology enhances the likelihood that cancer prevention will increasingly rely on chemoprevention. Chemoprevention, a new emerging science, means the use of agents to inhibit, delay or reverse carcinogenesis. Recent observations suggest a number of potential targets for chemoprevention. Many agents have potential benefit, but only modest chemopreventive efficacy in clinical trials. There is much evidence suggesting an inverse relationship between aspirin or NSAIDs consumption and CRC incidence and mortality. However, NSAID consumption is not problem-free, as 1997 data showed 107,000 hospitalisations and 16,500 deaths due to NSAIDs consumption in the US alone. Therefore, although chemoprevention of CRC is already possible, drugs that have more acceptable side-effect profiles than the currently available NSAIDs are required. COX-2-specific inhibitors, which have an improved safety profile, as compared to traditional NSAIDs that inhibit both the COX-1 and COX-2 enzymes, seem to be well suited drug candidates for CRC prevention. The inhibition of the growth of pre-cancerous and cancerous cells without affecting normal cells is the ultimate aim of cancer treatment and is of particular importance in chemoprevention studies, which may be long term in nature, involve healthy subjects and minimal toxicity. Cancer prevention is certain to be a significant focus of research and intervention in the coming years, propelled by the realization that we will be able to identify both individuals susceptible to specific cancers as well as the molecular targets that can alter or stop the carcinogenesis process. Pharmacology and genetics are collaborating to develop new chemoprevention agents designed to affect molecular targets linked to specific pre-malignant or predisposing conditions.

Animals↗
PubMed2004

Celecoxib but not rofecoxib inhibits the growth of transformed cells in vitro.

PURPOSE: Nonsteroidal anti-inflammatory drugs reduce the risk of colorectal cancer. The cyclooxygenase (COX) pathway of arachidonic acid metabolism is an important target for nonsteroidal anti-inflammatory drugs. Increased expression of COX-2 was recently shown to be an important step in the multistep process of colorectal cancer carcinogenesis. The new COX-2-specific inhibitors offer the benefit of cancer protection without the gastrointestinal toxicity reported for the old drugs. The purpose of this study was to compare the growth effects of two specific COX-2 inhibitors, celecoxib (Pfizer, Inc., New York, NY), and rofecoxib (Merck, White House Station, NJ) in normal and transformed enterocytes. EXPERIMENTAL DESIGN: Cultures of normal rat intestinal epithelial cell line, IEC-18, vector control cells, c-K-ras, c-K-ras-bak, and antisense-bak derivatives were treated with different dosages of celecoxib (0-60 micro M) and rofecoxib (0-20 micro M). Cell cycle analysis and apoptosis were assessed by fluorescence-activated cell sorting analysis. Protein expression was assessed by Western blot analysis and caspases 3 and 8 activities by ELISA. RESULTS: Celecoxib inhibited cell growth and induced apoptosis in a time- and dose-dependent manner. IEC18 parental cells were two to four times more resistant to celecoxib than ras, ras-bak, and antisense bak transformed cells that overexpress the COX-2 protein. The induction of apoptosis by celecoxib involved the caspase pathways. Rofecoxib, up to its maximal concentration of 20 micro M, did not inhibit cell growth or induce apoptosis. CONCLUSIONS: Celecoxib may prove to be a very efficient component in the prevention and treatment of gastrointestinal tumors because it inhibits the growth of cancerous cells without affecting the growth of normal cells.

Animals↗
PubMed2004

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.

Adenocarcinoma↗
PubMed2004

[Small bowel malignancies: why are they so rare?].

Cancer of the small-bowel is rare and comprises 2.4% of gastrointestinal malignancies. This is despite of its large mucosal surface area and its location between the stomach and the large bowel, two of the most common cancer sites. Nevertheless, there is a similarity between the disease and colorectal cancer. Therefore, it is of great interest to study the protective mechanisms of this organ and how tumor arises when these protectors fail. Among the risk factors for small bowel malignancies are Inflammatory Bowel Disease (IBD), familial syndromes, and lifestyle parameters (alcohol consumption, smoking, and high fat and animal protein diet). Due to the unusual symptoms, the rarity of the disease, and the difficulty in small bowel imaging, a correct diagnosis is often delayed. The treatment of choice, which allows full recovery, as in other malignancies of the gastrointestinal tract, is surgical resection of the tumor.

Diagnosis, Differential↗
PubMed2003

Oncogenic transformation of normal enterocytes by overexpression of cyclin D1.

Cyclin D1 plays an important role in the multi-step process of gastrointestinal tumorigenesis. We hypothesize that normal enterocytes over-expressing cyclin D1 will demonstrate a transformed phenotype. The nontumorigenic intestinal epithelial cell line, IEC-18, was transfected with the vector pMV7-CCND1, encoding cyclin D1. Three clones, with cyclin D1 levels similar to those seen in colon cancer cell lines, were further evaluated in comparison to the vector control cells. They proliferated faster and demonstrated anchorage-independent growth in soft agar, higher saturation density, and higher plating efficiency. When injected into nude mice, tumors were generated after 6-8 weeks. On the other hand these cells were more sensitive to induction of apoptosis. There was no change in the level of beta-catenin protein. In conclusion, cyclin D1 can act as an oncogene in vitro and in vivo, when produced in immortalized normal intestinal epithelial cells. This model may be useful for understanding the role and interrelationships of cyclin D1 in colorectal tumorigenesis.

Animals↗
PubMed2003

Cost-effectiveness of colorectal cancer screening in the average risk population.

Colorectal cancer (CRC) is a leading cause of cancer death in North America and in Israel. Risk of CRC increases exponentially with age starting at the age of 50 years. Therefore, people older than 50 years are being considered as an average risk population for CRC. The objective of this study was to obtain an improved assessment of the cost-effectiveness analysis of screening for CRC in the average risk population by using a more accurate technique, namely the Partially Observed Markov Decision Process (POMDP). We conducted a cost-effectiveness analysis within the specific probability rates and costs in Israel. This study revealed that it is highly cost-effective to screen average-risk asymptomatic individuals.

Algorithms↗
PubMed2003

[Prevention and early detection of colorectal cancer in average risk population--summary of a meeting and the Israeli gastroenterology policy].

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality, with a lifetime risk of 5-6% and mortality rate of nearly 50%. About 75% of the cases occur in average-risk individuals. CRC ideally fulfills the criteria for organizing a mass-screening program: It is common and lethal, cancer is preceded by a pre-malignant lesion (adenoma) and transition from precursor to malignancy develops over years, providing an opportunity for intervention. It is well established that removal of adenomas (polypectomy) prevents CRC and CRC-related death in up to 90% of the cases. In Israel, we lack a clear policy for CRC screening and prevention by the health authorities. A meeting on this subject was held at the Israel Cancer Association, attended by the Minister of Health and leading figures in gastroenterology, oncology and public health. AIMS: To summarize the meeting and the Israeli Gastroenterology Association policy. SUMMARY: Current data on fecal occult blood test, sigmoidoscopy, and colonoscopy was presented, including the reduction of cancer incidence and mortality, safety and cost-effectiveness of each modality. Worldwide and Israeli results on colonoscopy in average-risk persons age 50-75, demonstrated a considerable prevalence of neoplasia, a low morbidity rate, no mortality and a high cost-effectiveness. Based on these results and the literature evidence of up to 90% reduction of CRC mortality following colonoscopy, CRC justifies all the criteria for organizing a prevention program by the health authorities for average-risk population age 50-75. Screening colonoscopy for CRC prevention should be included in this program.

Aged↗
PubMed2003

The I1307K adenomatous polyposis coli gene variant does not contribute in the assessment of the risk for colorectal cancer in Ashkenazi Jews.

Ashkenazi Jews with the I1307K adenomatous polyposis coli gene variant were suggested to confer a higher risk for colorectal cancer (CRC). We assessed the clinical importance of this polymorphism in Israeli Jews at average and elevated risk for CRC. Among 1,370 consecutive subjects that were examined, 975 Ashkenazi Jews were stratified into those at average risk (no personal or family history of colorectal neoplasia) and those at high risk. DNA was obtained from peripheral leukocytes and amplified by PCR, with primers designed to detect the I1307K variant. Overall, I1307K polymorphism was found in 7.1% (9.1% among Ashkenazi and 1.7% among non-Ashkenazi Jews). The carrier rate was 8.3 and 9.3% in average and high-risk Ashkenazim, respectively (P = 0.65). The overall odds ratio for neoplasia in carriers was 1.43 (95% confidence interval, 0.89-2.30). Age, gender, and the histopathological features of adenomas and cancers did not differ between carriers and noncarriers. No interaction on the CRC risk was found between I1307K variant and lifestyle modifiers (such as cigarette smoking, alcohol consumption, high body mass index, low physical activity, and vitamins/antioxidant intake). The I1307K adenomatous polyposis coli gene variant is not an important marker for increased risk for CRC. It confirms previous reports of a slight nonsignificant increase (OR, 1.4) in the risk of CRC in these carriers. There is no interaction effect on the risk of colorectal neoplasia between the I1307K variant and various lifestyle risk factors. The usual recommended screening and surveillance strategies should be used for carriers of this polymorphism.

Adenomatous Polyposis Coli Protein↗
PubMed2003

[Virtual colonoscopy in real life--is it that good?].

BACKGROUND: Colon cancer is the main cause of mortality among the gastrointestinal cancers in Israel. Early detection of the average risk population is recommended from the age of 50 to 75 years. Private departments of radiology aggressively advertise virtual colonoscopy for the early detection of colon cancer, although it is not recognised as such in any country. METHODS: We collected all cases in which virtual colonoscopy was followed by endoscopic colonoscopy in the same patient from four medical centers in Israel. RESULTS: Total discrepancy between the results of the two examinations was found in 2/3 of the patients. In some cases colon cancer was missed. CONCLUSIONS: The results presented herein, raise many questions and "red lights" as to the use of virtual colonoscopy in its present form for screening purposes in Israel unless it is in the setting of clinical research.

Advertising↗
PubMed2002

Superiority of a functional leukocyte adhesiveness/aggregation test over the white blood cell count to discriminate between mild and significant inflammatory response in patients with acute bacterial infections.

Electronic cell counters may underestimate the white blood cell count (WBCC) in the presence of aggregated leukocytes. In the present study we focused on the possibility of using a functional, as opposed to an anatomic, count to circumvent this eventual underestimation. A model of bacterial infection was used because of the importance of leukocytosis in the physician's clinical decision-making process. There were 35 patients with low C-reactive protein (CRP) concentrations (0.5-4.9 mg/dL), 45 with intermediate (5-9.9 mg/dL), and 120 with relatively high (>10 mg/dL) CRP concentrations. A significant (P=0.008) difference was noted between the state of leukocyte adhesiveness/aggregation in the peripheral blood of individuals with low CRP concentrations (3.5%+/-4.3%) and those with high CRP concentrations (7.4%+/-8%), while there was no significant difference in the respective number of WBCs per cubic millimeter (cmm) (11,600 +/- 5,500 and 14,000 +/- 7,200, respectively). We raise the possibility that a functional test might be superior over an anatomic count in patients with acute bacterial infection and a significant acute phase response.

Adhesiveness↗
PubMed2002

The erythrocyte adhesiveness/aggregation test to reveal real-time information of rheological relevance in patients with familial and primary hypercholesterolemia before and following plasma exchange.

We applied an erythrocyte adhesiveness/aggregation test (EAAT) to a model of plasma exchange in individuals with familial and primary hypercholesterolemia. The significant (p < 0.0001) reduction in the concentration of fibrinogen by 56%, globulins by 48%, and cholesterol by 53% corresponded to the expected significant (p < 0.0001) reduction in the degree of erythrocyte adhesiveness/aggregation in the peripheral venous blood. By virtue of its being a real-time, simple, very-low-cost, and essentially bedside technique, the EAAT might have the potential of disclosing information of rheological relevance immediately before, during, as well as following apheretical procedures administered to patients with an impaired rheological profile.

Adhesiveness↗
PubMed2002

The role of nutrition and chemoprevention in colorectal cancer: from observations to expectations.

During the last 20 years the role of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) in reducing the risk of colorectal cancer was shown in more than 100 animal studies. Support derives from 23 of 25 epidemiological studies confirming this protective effect. The COX-2 specific inhibitors and the selective apoptotic anti-neoplastic drugs offer the benefit of cancer protection without the gastrointestinal toxicity that was reported for the 'old' drugs. The presence of multiple molecular targets offers the potential for combination. The pivotal question in the puzzle of NSAID chemopreventive treatment should not be 'if' but 'how'. The concept that different food components may initiate or prevent cancer was illustrated by different epidemiological studies and animal models. Yet the chemical and biological complexity of the food, the difficulty in measuring habitual diets and the unavoidable changes in food constituents following a specific change in diet all contribute to this complexity.

Animals↗