Background: Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay betw... more Background: Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. Apart from the Major Histocompatibility locus which is the main contributor to risk susceptibility, more than 40 loci are recognized. One among these is the CTLA-4, however data from the literature are controversial. The aim of our study was to investigate the role of CTLA4 49 A/G as a risk susceptibility factor for the development of type 1 diabetes in a cohort of Egyptian families. Subjects and methods: This is a case control study including 88 Egyptian families with one or more index cases (<18 years). The control group comprised 369 healthy unrelated subjects with no family history of diabetes or autoimmune disease. Using PCR-RFLP methodology, CTLA4 49 A/G was analyzed in 738 samples representing 88 families (88 patients, 125 siblings and 156 parents) and 369 control. Results: The age of onset was 6 days-12.5 years with a mean of 5.3 ± 3.6 and a median of 5 years. The mode of presentation was classic symptoms in 51 and diabetic ketoacidosis in 37 cases.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights
Purpose: The particular goal of this work is to study some cell cycle regulatory proteins and the... more Purpose: The particular goal of this work is to study some cell cycle regulatory proteins and their potential impact on prognosis of breast cancer; p53, cyclin D1 and p27 are potential effectors being the major contributors to the control of the restriction (R) check point of the cell cycle. We also aimed to evaluate different techniques used to detect these cell cycle proteins. Material and Methods: Forty five breast cancer patients as well as 10 controls with non malignant pathology were assessed for cell cycle regulators each by 2 different techniques; p53 was assessed by enzyme immunoassay (EIA) and immunohistochemistry (IHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by WB and IHC. The cutoff was calculated as the mean of the normal controls +2 SD. Patients were followed up for 4 years and their laboratory data were correlated with different clinical parameters and with other studied regulators. Results: Eighty seven percent of cases (39/45) were positive for p53 by EIA with a range from 20 to 4300, and a mean of 464±971pg/mg protein. By IHC, 80% (24/30) of the cases showed varying degrees of positivity. Using WB, cyclin D1 showed high expression levels above cut off values in 69% of patients (31/45) and in 67% (20/30) by IHC. The corresponding positive figures for p27 were 82% (37/45) and 73% (22/30) using the two techniques, respectively. No significant association was found between p53, cyclin D1 and p27 on one side and different clinical parameters as lymph node status, tumor size or presence of distant metastases on the other side. Survival was poor in patients with high p53 expression. Cyclin D1 positive cases showed comparable survival with negative cases, whereas high p27 levels favored a longer disease free survival. Conclusions: Techniques more suitable for assessment of each of these markers in our consideration were EIA 93 for p53, WB for cyclin D1 and IHC for p27. Moreover, this study demonstrated that these markers were relevant to the biological behavior of the tumor cell per se with a possible impact on prognosis and survival, independent of other clinical prognostic factors.
A comparative study to determine HLA allele frequency in the Egyptian population Azza Kamel 1, Na... more A comparative study to determine HLA allele frequency in the Egyptian population Azza Kamel 1, Nayera Hamdy 1, Ghada Mossallam 1, Sally Elfishawi 1, Yasser Elnahass 1, Alaa Elhaddad 1 Hossam Kamel 1 1National cancer institute, Cairo, Egypt Determination of HLA allele and haplotype frequencies in different ethnic groups is useful for population genetic analyses, to study the relationship among these populations and in unrelated donor search for Hematopoietic stem cell transplantation (HSCT).Egypt is the largest Arab and Middle East country in population size with an estimate of 92 million :this entails the use of large pool of individuals to represent all HLA alleles present in the population Many studies use HSCT unrelated donors’ HLA genotype as a representative sample for HLA allele frequency of the given population yet few studies used related large pool of donors for such a purpose. The rationale behind the present study was to compare HLA allele between two groups, the first is...
The Egyptian journal of immunology / Egyptian Association of Immunologists, 2005
Risk factors affecting asymptomatic HCV carriers as well as intrafamilial HCV transmission are no... more Risk factors affecting asymptomatic HCV carriers as well as intrafamilial HCV transmission are not completely known. We hypothesized that immunological factors related to HLA profiles may affect the intrafamilial transmission. We investigated the possible association between HLA class I & II genes and the presence of HCV infection, as well as their possible role in intrafamilial tramsmition. One hundred forty five individuals comprising 40 families were recruited from bone marrow transplantation (BMT) unit at the National Cancer Institute, Cairo University. Serologic class I and generic class II MHC alleles were determined. Hepatitis C virus was detected by enzyme immunoassay (EIA) and confirmed by INNO-LIA. Detection of viral RNA was also confirmed by RT-PCR and HCV genotyping was done by immunoblotting (INNO-LiPA) and direct sequencing by TrueGene kit. Out of the 145 serum samples, 33 were positive for HCV antibodies by EIA and confirmed by both immunoblotting techniques and RT-PC...
Journal of the Egyptian National Cancer Institute, 2007
ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia a... more ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia are unknown and are likely to involve an interaction between genetic and environmental factors. Therefore, unfavourable gene-environmental interactions might be involved in the genesis of ALL. The aim of this work was to evaluate, in a case-control study, whether the common polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR) namely (C677T and A1298C) and methionine synthase (MS) (A2756G) genes may play a role in altering susceptibility to pediatric ALL as individual genes and in combination. DNA of 88 ALL patients (age < or = 18 years) and 311 healthy control subjects was analyzed for the polymorphisms of MTHFR and MS genes using PCR-RFLP method. The frequencies of the wild types of MTHFR 677CC, MTHFR 1298AA and MS 2756AA, the homozygous genotypes of MTHFR 677TT, MTHFR 1298CC and MS 2756GG and heterozygous genotypes of MTHFR 677CT and MS 2756AG showed no statistically si...
SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acut... more SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acute lymphoblastic leukemia (T-ALL). Since the frequency of T-ALL appears to be relatively higher in developing countries, we wished to determine as to what fraction of T-ALL from this population harbor SCL rearrangements. We show in this study that although the overall frequency of SCL/SIL rearrangements in T-ALL is similar to the Western countries this is at the expense of increased type A rearrangements. Whether the paucity of type B rearrangements reflects a difference in disease etiology in this part of the world is to be determined.
Abstract: Background: Mercaptopurine is one of the most important drugs used in cancer treatment.... more Abstract: Background: Mercaptopurine is one of the most important drugs used in cancer treatment. Its elimination depends mainly on the enzyme Thiopurine S-methyl Transferase (TPMT). A number of known genetic polymorphisms can affect the activity of this enzyme. ...
To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors&amp;am... more To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; institute and to define significant prognostic factors. This study included 154 children with newly diagnosed ALL below the age of 18 years during the period August 1, 1998, to December 31, 2000. All patients were treated according to the NCI, Cairo, Egypt, treatment protocol modified from study XIII for high-risk ALL of St. Jude Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Research Hospital. B-cell precursor phenotype was encountered in 73.4% of patients, T-cell in 26.6%. According to NCI/Rome criteria for risk classification, 58.4% of patients were in the high-risk group (90% of T-lineage compared with 47% of B-lineage ALL, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Nine patients (5.8%) died during induction and 10 patients (6.5%) failed to achieve remission. With a median follow-up of 43 months, the 3-year disease-free survival and its probability at 5 years were 80 +/- 3.6% and 75.3 +/- 4%, respectively; the 3-year event-free survival and its probability at 5 years were 69 +/- 3.8% and 65.2 +/- 4%, respectively. B-cell precursor ALL had 5-year probabilities of disease-free survival and event-free survival of 80.5 +/- 4% and 71.8 +/- 4.5% compared with 60.2 +/- 8.6% and 46.7 +/- 8% for T-cell, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, log-rank test). Prognostic factors that had a statistically significant unfavorable impact on survival by univariate analysis were age 10 years or more, central nervous system involvement, T-lineage phenotype, high-risk group, DNA index less than 1.16, and slow early response to treatment. By multivariate analysis, central nervous system involvement, high-risk group, and slow early response to treatment still had prognostic significance. Risk classification demonstrated prognostic significance for B-lineage but not T-lineage ALL. This treatment protocol was effective in improving ALL survival among patients at the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; institute compared with previous trials, although the outcome remains lower than that in more industrialized countries. Prognostic factors defined in this study were similar to those identified by other cooperative groups.
Objective: The c-kit proto-oncogene encodes a 145 KDa tyrosine kinase transmembrane receptor that... more Objective: The c-kit proto-oncogene encodes a 145 KDa tyrosine kinase transmembrane receptor that binds stem cell factor (SCF). The c-kit has been classified as CD117 and the monoclonal antibody is claimed to be useful in immunophenotyping of ...
Background: Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay betw... more Background: Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. Apart from the Major Histocompatibility locus which is the main contributor to risk susceptibility, more than 40 loci are recognized. One among these is the CTLA-4, however data from the literature are controversial. The aim of our study was to investigate the role of CTLA4 49 A/G as a risk susceptibility factor for the development of type 1 diabetes in a cohort of Egyptian families. Subjects and methods: This is a case control study including 88 Egyptian families with one or more index cases (<18 years). The control group comprised 369 healthy unrelated subjects with no family history of diabetes or autoimmune disease. Using PCR-RFLP methodology, CTLA4 49 A/G was analyzed in 738 samples representing 88 families (88 patients, 125 siblings and 156 parents) and 369 control. Results: The age of onset was 6 days-12.5 years with a mean of 5.3 ± 3.6 and a median of 5 years. The mode of presentation was classic symptoms in 51 and diabetic ketoacidosis in 37 cases.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights
Purpose: The particular goal of this work is to study some cell cycle regulatory proteins and the... more Purpose: The particular goal of this work is to study some cell cycle regulatory proteins and their potential impact on prognosis of breast cancer; p53, cyclin D1 and p27 are potential effectors being the major contributors to the control of the restriction (R) check point of the cell cycle. We also aimed to evaluate different techniques used to detect these cell cycle proteins. Material and Methods: Forty five breast cancer patients as well as 10 controls with non malignant pathology were assessed for cell cycle regulators each by 2 different techniques; p53 was assessed by enzyme immunoassay (EIA) and immunohistochemistry (IHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by WB and IHC. The cutoff was calculated as the mean of the normal controls +2 SD. Patients were followed up for 4 years and their laboratory data were correlated with different clinical parameters and with other studied regulators. Results: Eighty seven percent of cases (39/45) were positive for p53 by EIA with a range from 20 to 4300, and a mean of 464±971pg/mg protein. By IHC, 80% (24/30) of the cases showed varying degrees of positivity. Using WB, cyclin D1 showed high expression levels above cut off values in 69% of patients (31/45) and in 67% (20/30) by IHC. The corresponding positive figures for p27 were 82% (37/45) and 73% (22/30) using the two techniques, respectively. No significant association was found between p53, cyclin D1 and p27 on one side and different clinical parameters as lymph node status, tumor size or presence of distant metastases on the other side. Survival was poor in patients with high p53 expression. Cyclin D1 positive cases showed comparable survival with negative cases, whereas high p27 levels favored a longer disease free survival. Conclusions: Techniques more suitable for assessment of each of these markers in our consideration were EIA 93 for p53, WB for cyclin D1 and IHC for p27. Moreover, this study demonstrated that these markers were relevant to the biological behavior of the tumor cell per se with a possible impact on prognosis and survival, independent of other clinical prognostic factors.
A comparative study to determine HLA allele frequency in the Egyptian population Azza Kamel 1, Na... more A comparative study to determine HLA allele frequency in the Egyptian population Azza Kamel 1, Nayera Hamdy 1, Ghada Mossallam 1, Sally Elfishawi 1, Yasser Elnahass 1, Alaa Elhaddad 1 Hossam Kamel 1 1National cancer institute, Cairo, Egypt Determination of HLA allele and haplotype frequencies in different ethnic groups is useful for population genetic analyses, to study the relationship among these populations and in unrelated donor search for Hematopoietic stem cell transplantation (HSCT).Egypt is the largest Arab and Middle East country in population size with an estimate of 92 million :this entails the use of large pool of individuals to represent all HLA alleles present in the population Many studies use HSCT unrelated donors’ HLA genotype as a representative sample for HLA allele frequency of the given population yet few studies used related large pool of donors for such a purpose. The rationale behind the present study was to compare HLA allele between two groups, the first is...
The Egyptian journal of immunology / Egyptian Association of Immunologists, 2005
Risk factors affecting asymptomatic HCV carriers as well as intrafamilial HCV transmission are no... more Risk factors affecting asymptomatic HCV carriers as well as intrafamilial HCV transmission are not completely known. We hypothesized that immunological factors related to HLA profiles may affect the intrafamilial transmission. We investigated the possible association between HLA class I & II genes and the presence of HCV infection, as well as their possible role in intrafamilial tramsmition. One hundred forty five individuals comprising 40 families were recruited from bone marrow transplantation (BMT) unit at the National Cancer Institute, Cairo University. Serologic class I and generic class II MHC alleles were determined. Hepatitis C virus was detected by enzyme immunoassay (EIA) and confirmed by INNO-LIA. Detection of viral RNA was also confirmed by RT-PCR and HCV genotyping was done by immunoblotting (INNO-LiPA) and direct sequencing by TrueGene kit. Out of the 145 serum samples, 33 were positive for HCV antibodies by EIA and confirmed by both immunoblotting techniques and RT-PC...
Journal of the Egyptian National Cancer Institute, 2007
ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia a... more ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia are unknown and are likely to involve an interaction between genetic and environmental factors. Therefore, unfavourable gene-environmental interactions might be involved in the genesis of ALL. The aim of this work was to evaluate, in a case-control study, whether the common polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR) namely (C677T and A1298C) and methionine synthase (MS) (A2756G) genes may play a role in altering susceptibility to pediatric ALL as individual genes and in combination. DNA of 88 ALL patients (age < or = 18 years) and 311 healthy control subjects was analyzed for the polymorphisms of MTHFR and MS genes using PCR-RFLP method. The frequencies of the wild types of MTHFR 677CC, MTHFR 1298AA and MS 2756AA, the homozygous genotypes of MTHFR 677TT, MTHFR 1298CC and MS 2756GG and heterozygous genotypes of MTHFR 677CT and MS 2756AG showed no statistically si...
SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acut... more SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acute lymphoblastic leukemia (T-ALL). Since the frequency of T-ALL appears to be relatively higher in developing countries, we wished to determine as to what fraction of T-ALL from this population harbor SCL rearrangements. We show in this study that although the overall frequency of SCL/SIL rearrangements in T-ALL is similar to the Western countries this is at the expense of increased type A rearrangements. Whether the paucity of type B rearrangements reflects a difference in disease etiology in this part of the world is to be determined.
Abstract: Background: Mercaptopurine is one of the most important drugs used in cancer treatment.... more Abstract: Background: Mercaptopurine is one of the most important drugs used in cancer treatment. Its elimination depends mainly on the enzyme Thiopurine S-methyl Transferase (TPMT). A number of known genetic polymorphisms can affect the activity of this enzyme. ...
To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors&amp;am... more To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; institute and to define significant prognostic factors. This study included 154 children with newly diagnosed ALL below the age of 18 years during the period August 1, 1998, to December 31, 2000. All patients were treated according to the NCI, Cairo, Egypt, treatment protocol modified from study XIII for high-risk ALL of St. Jude Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Research Hospital. B-cell precursor phenotype was encountered in 73.4% of patients, T-cell in 26.6%. According to NCI/Rome criteria for risk classification, 58.4% of patients were in the high-risk group (90% of T-lineage compared with 47% of B-lineage ALL, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Nine patients (5.8%) died during induction and 10 patients (6.5%) failed to achieve remission. With a median follow-up of 43 months, the 3-year disease-free survival and its probability at 5 years were 80 +/- 3.6% and 75.3 +/- 4%, respectively; the 3-year event-free survival and its probability at 5 years were 69 +/- 3.8% and 65.2 +/- 4%, respectively. B-cell precursor ALL had 5-year probabilities of disease-free survival and event-free survival of 80.5 +/- 4% and 71.8 +/- 4.5% compared with 60.2 +/- 8.6% and 46.7 +/- 8% for T-cell, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, log-rank test). Prognostic factors that had a statistically significant unfavorable impact on survival by univariate analysis were age 10 years or more, central nervous system involvement, T-lineage phenotype, high-risk group, DNA index less than 1.16, and slow early response to treatment. By multivariate analysis, central nervous system involvement, high-risk group, and slow early response to treatment still had prognostic significance. Risk classification demonstrated prognostic significance for B-lineage but not T-lineage ALL. This treatment protocol was effective in improving ALL survival among patients at the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; institute compared with previous trials, although the outcome remains lower than that in more industrialized countries. Prognostic factors defined in this study were similar to those identified by other cooperative groups.
Objective: The c-kit proto-oncogene encodes a 145 KDa tyrosine kinase transmembrane receptor that... more Objective: The c-kit proto-oncogene encodes a 145 KDa tyrosine kinase transmembrane receptor that binds stem cell factor (SCF). The c-kit has been classified as CD117 and the monoclonal antibody is claimed to be useful in immunophenotyping of ...
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