The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a ... more The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20–85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign can...
Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant propertie... more Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] and in patients with ulcerative colitis (UC). Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo the treated group ( < 0.05). Selenium was the more active component. The contribution of gree...
There is increasing evidence to suggest that acetylsalicylic acid (ASA) and other nonsteroidal an... more There is increasing evidence to suggest that acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumours per animal and fewer animals with tumours after administration of several different NSAIDs. Studies in humans consistently support this hypothesis. Intervention data from familial adenomatosis coli establish that the process of human colonic adenoma polyp formation is affected. Supportive evidence comes from 21 of 23 human studies -- both case-control and cohort. The reduced risk has been found in men and women, for cancers of the colon and the rectum and for the use of both ASA and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. The molecular mechanisms responsible for the chemopreventive action of this class of drugs is not completely established. Protection may affec...
CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can ... more CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8–83.2%) and 83.8% (95% CI, 74.6–92.7%) and for adenomas 84.2% (95% CI, 60.4–96.4%) and 73.5% (95% CI, 61.4–83.5%), respectively. In the second trial (n= 149),...
Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. G... more Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. Guided by the identification of the SLC3A1 amino acid-transport gene on chromosome 2, we recently established genetic linkage of cystinuria to chromosome 2p in 17 families, without evidence for locus heterogeneity. Other authors have independently identified missense mutations in SLC3A1 in cystinuria patients. In this report we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical amino acid change, and a nonsense mutation. The latter stop codon was found in all of eight Ashkenazi Jewish carrier chromosomes examined. This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cystinuria families.
Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal can... more Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50...
ABSTRACT Previous experimental epidemiologic and clinical studies have shown a significant reduct... more ABSTRACT Previous experimental epidemiologic and clinical studies have shown a significant reduction in colorectal cancer occurrence and mortality among individuals taking NSAIDs. NSAIDs inhibit the enzymatic activity of both isoforms of cyclo-oxygenase (COX-1 and COX-2), which regulate prostaglandin synthesis. COX-2 is an inducible enzyme that is overexpressed at sites of inflammation and in several epithelial cancers. Several studies have indicated that COX-2 overexpression appears to be involved in tumorigenesis by promoting cell division and proliferation, inhibiting apoptosis, stimulating angiogenesis, altering cell adhesion, and enhancing tumor cell invasiveness. Blocking of these activities by COX-2 selective inhibitors is considered the main mechanism that explains the anticarcinogenic effect of COX-2 selective inhibitors. In addition, other independent COX-2 mechanisms have been described.Treatment with selective COX-2 inhibitors has shown promising results in the suppression of colon polyps, both in animal models for familial adenomatous polyposis (FAP) and in patients with FAP, and recent clinical studies have identified the potential benefit of these agents for colon cancer chemoprevention. However, serious concerns have been raised regarding the potential adverse effects of long-term selective COX-2 inhibitor use, most notably those within the cardiovascular system, such as myocardial infarctions, strokes, and increased blood pressure.The role of COX-2 inhibitors in cancer chemoprevention is still evolving and a careful risk/benefit analysis of the recent clinical studies would mandate the precise clinical setting that these drugs can be used in.
Background: We have shown that CD24, a cell surface molecule, is overexpressed early in the multi... more Background: We have shown that CD24, a cell surface molecule, is overexpressed early in the multistep process of colorectal neoplasia (Gastroenterology, 2006) hence, it can serve as a target for early detection and immunotherapy. The anti-CD24 murine SWA11 Mab (generous gift from Prof. Sthal, Zurich University) binds to CD24 and inhibits tumor cell growth, in vitro and in vivo, in a time- and dose-dependent manner (Cancer Research, 2008). However, murine Mabs have limitations because of their xenogeneic nature and due to the human anti-mouse antibody (HAMA) response. Aim: To produce an improved, chimeric form of the SWA11 Mab. Methods: Mammalian vector pMAZ-IgH for human γ1 heavy-chain and pMAZ-IgL for human κ light chain expression were designed. The variable region genes encoding the murine anti-CD24 SWA11 MAb were cloned for expression as chimeric γ1/kappa antibody into the mammalian pMAZ-IgH and pMAZ-IgL expression vectors and co-transfected into HEK293 cells. Stable clones were...
Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vita... more Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25- hydroxyvitamin D (25-OH D3). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D (1,25-(OH)2 D3), which interacts with nuclear vitamin
Epidemiological data, family history, clinical data, and HLA typing were studied in three groups ... more Epidemiological data, family history, clinical data, and HLA typing were studied in three groups of patients with Behçet's syndrome: six Israeli Ashkenazi Jews, 29 non-Ashkenazi Jews, and three Israeli Arabs. HLA-B51 and B52 were present in 24/38 (63%) and 8/38 (21%), respectively, of the patients compared with 13/151 (9%) of the control group for both cases, a relative risk of
Apoptosis : an international journal on programmed cell death, 1999
It is now apparent that apoptosis is closely linked to the control of cell cycle progression. Dur... more It is now apparent that apoptosis is closely linked to the control of cell cycle progression. During the G1 to S progression, cyclin D1, p53, and the cyclin dependent kinase inhibitors p21WAF1 and p27kip1 can play roles in induction of apoptosis. During the G2 and M phases, premature activation of Cdk1 can cause cells to enter mitotic catastrophe, which results in apoptosis. In this review we focus on factors acting during G1 and S, particularly cyclin D1, and their effects on cell growth, senescence and apoptosis. We emphasize that cyclin D1 can have diverse effects on cells depending on its level of expression, the specific cell type, the cell context and other factors. Possible mechanisms by which cyclin D1 exerts these diverse effects, via cyclin dependent kinase-dependent and -independent pathways, are discussed.
The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a ... more The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20–85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign can...
Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant propertie... more Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] and in patients with ulcerative colitis (UC). Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo the treated group ( < 0.05). Selenium was the more active component. The contribution of gree...
There is increasing evidence to suggest that acetylsalicylic acid (ASA) and other nonsteroidal an... more There is increasing evidence to suggest that acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumours per animal and fewer animals with tumours after administration of several different NSAIDs. Studies in humans consistently support this hypothesis. Intervention data from familial adenomatosis coli establish that the process of human colonic adenoma polyp formation is affected. Supportive evidence comes from 21 of 23 human studies -- both case-control and cohort. The reduced risk has been found in men and women, for cancers of the colon and the rectum and for the use of both ASA and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. The molecular mechanisms responsible for the chemopreventive action of this class of drugs is not completely established. Protection may affec...
CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can ... more CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8–83.2%) and 83.8% (95% CI, 74.6–92.7%) and for adenomas 84.2% (95% CI, 60.4–96.4%) and 73.5% (95% CI, 61.4–83.5%), respectively. In the second trial (n= 149),...
Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. G... more Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. Guided by the identification of the SLC3A1 amino acid-transport gene on chromosome 2, we recently established genetic linkage of cystinuria to chromosome 2p in 17 families, without evidence for locus heterogeneity. Other authors have independently identified missense mutations in SLC3A1 in cystinuria patients. In this report we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical amino acid change, and a nonsense mutation. The latter stop codon was found in all of eight Ashkenazi Jewish carrier chromosomes examined. This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cystinuria families.
Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal can... more Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50...
ABSTRACT Previous experimental epidemiologic and clinical studies have shown a significant reduct... more ABSTRACT Previous experimental epidemiologic and clinical studies have shown a significant reduction in colorectal cancer occurrence and mortality among individuals taking NSAIDs. NSAIDs inhibit the enzymatic activity of both isoforms of cyclo-oxygenase (COX-1 and COX-2), which regulate prostaglandin synthesis. COX-2 is an inducible enzyme that is overexpressed at sites of inflammation and in several epithelial cancers. Several studies have indicated that COX-2 overexpression appears to be involved in tumorigenesis by promoting cell division and proliferation, inhibiting apoptosis, stimulating angiogenesis, altering cell adhesion, and enhancing tumor cell invasiveness. Blocking of these activities by COX-2 selective inhibitors is considered the main mechanism that explains the anticarcinogenic effect of COX-2 selective inhibitors. In addition, other independent COX-2 mechanisms have been described.Treatment with selective COX-2 inhibitors has shown promising results in the suppression of colon polyps, both in animal models for familial adenomatous polyposis (FAP) and in patients with FAP, and recent clinical studies have identified the potential benefit of these agents for colon cancer chemoprevention. However, serious concerns have been raised regarding the potential adverse effects of long-term selective COX-2 inhibitor use, most notably those within the cardiovascular system, such as myocardial infarctions, strokes, and increased blood pressure.The role of COX-2 inhibitors in cancer chemoprevention is still evolving and a careful risk/benefit analysis of the recent clinical studies would mandate the precise clinical setting that these drugs can be used in.
Background: We have shown that CD24, a cell surface molecule, is overexpressed early in the multi... more Background: We have shown that CD24, a cell surface molecule, is overexpressed early in the multistep process of colorectal neoplasia (Gastroenterology, 2006) hence, it can serve as a target for early detection and immunotherapy. The anti-CD24 murine SWA11 Mab (generous gift from Prof. Sthal, Zurich University) binds to CD24 and inhibits tumor cell growth, in vitro and in vivo, in a time- and dose-dependent manner (Cancer Research, 2008). However, murine Mabs have limitations because of their xenogeneic nature and due to the human anti-mouse antibody (HAMA) response. Aim: To produce an improved, chimeric form of the SWA11 Mab. Methods: Mammalian vector pMAZ-IgH for human γ1 heavy-chain and pMAZ-IgL for human κ light chain expression were designed. The variable region genes encoding the murine anti-CD24 SWA11 MAb were cloned for expression as chimeric γ1/kappa antibody into the mammalian pMAZ-IgH and pMAZ-IgL expression vectors and co-transfected into HEK293 cells. Stable clones were...
Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vita... more Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25- hydroxyvitamin D (25-OH D3). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D (1,25-(OH)2 D3), which interacts with nuclear vitamin
Epidemiological data, family history, clinical data, and HLA typing were studied in three groups ... more Epidemiological data, family history, clinical data, and HLA typing were studied in three groups of patients with Behçet's syndrome: six Israeli Ashkenazi Jews, 29 non-Ashkenazi Jews, and three Israeli Arabs. HLA-B51 and B52 were present in 24/38 (63%) and 8/38 (21%), respectively, of the patients compared with 13/151 (9%) of the control group for both cases, a relative risk of
Apoptosis : an international journal on programmed cell death, 1999
It is now apparent that apoptosis is closely linked to the control of cell cycle progression. Dur... more It is now apparent that apoptosis is closely linked to the control of cell cycle progression. During the G1 to S progression, cyclin D1, p53, and the cyclin dependent kinase inhibitors p21WAF1 and p27kip1 can play roles in induction of apoptosis. During the G2 and M phases, premature activation of Cdk1 can cause cells to enter mitotic catastrophe, which results in apoptosis. In this review we focus on factors acting during G1 and S, particularly cyclin D1, and their effects on cell growth, senescence and apoptosis. We emphasize that cyclin D1 can have diverse effects on cells depending on its level of expression, the specific cell type, the cell context and other factors. Possible mechanisms by which cyclin D1 exerts these diverse effects, via cyclin dependent kinase-dependent and -independent pathways, are discussed.
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Papers by Nadir Arber