HLA-B*58 and HLA-B*27 Play a Role in the Development of Acute Leukemia: A Case Control Study.

BACKGROUND: Acute leukemia (AL) constitutes a group of malignant hematological diseases with multifactor origins. Some human leukocyte alleles (HLA) may be important genetic risk factors for development of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It is still unknown whether there is a relationship between ALL and AML with some alleles of the major histocompatibility complex. Our study looks specifically at western and southwest Algerian populations. METHOD: Using the polymerase chain reaction with the sequence specific probe (PCR- SSP) method, we investigated the relationship of HLA-B alleles in 163 Algerian AL patients and 293 controls from the same ethnic origin. The study ran from 2013 - 2020. RESULTS: Allele frequencies of HLA-B*27 and HLA-B*58 was higher in AL patients compared with control individuals; p=0.05 and p=0.03 respectively. Interestingly, all patients carrying HLA-B*27 allele and 88% of patients carrying HLA-B*58 allele had AML. However, there were no significant differences when we compared these results with the rest of AL group (HLA-B*X allele) (p=0.387). Response to induction chemotherapy treatment were comparable between the two patient groups 67% and 65% (p=0.978) respectively. CONCLUSION: These results suggest that the HLA-B*27 and HLA-B*58, may be factors predisposing individuals to acute leukemia, in west and southwest Algerian patients. A large-scale study is still needed to confirm these findings.

A Distinct Anti-EBV DNase Profile in Patients with Undifferentiated Nasopharyngeal Carcinoma Compared to Classical Antigens.

Nasopharyngeal cancer (NPC) is a prevalent type of cancer that often takes the form of undifferentiated carcinoma in the Maghreb region. It affects people of all ages. NPC diagnosis, mainly based on detecting Epstein-Barr virus (EBV), has not been well evaluated in North Africa. We compared the classical EBV serological tests using indirect immunofluorescence to the detection of EBV DNase antibodies by immunoblot in Algerian NPC patients. Significant variations were observed among different age groups of patients regarding the presence of VCA-IgA antibodies (0-14 and ≥30 years old, p < 0.0001; 15-19 and ≥30 years old, p < 0.01) and EA-IgA (0-14 and ≥30 years old, p < 0.01; 15-29 and ≥30 years old, p < 0.05). Differences were also noted in the titers of IgA anti-VCA and anti-EA antibodies across the three age groups. Some patients under the age of 30 with detectable IgG anti-VCA antibodies had undetectable IgA anti-VCA antibodies. These patients had a strong anti-DNase IgA response. However, older individuals had a higher level of anti-DNase IgG. Before treatment, children had strong DNase reactivity as indicated by specific IgA antibodies. Young adults had high IgA anti-DNase response, but the elderly (90.9%) had a lower response for these antibodies. Following therapy, the children retained high levels of IgA anti-DNase antibodies, and 66% of the young adults demonstrated robust antibody reactivity against DNase. In contrast, IgG responses to anti-DNase were low in children. This study demonstrated the utility of anti-DNase responses in the diagnosis and prognosis of NPC.

Expression profile of interleukin-6, 4-hydroxy-2-nonenal, and hypoxia-inducible factor 1-α in women with breast cancer and their association with clinicopathological parameters.

Introduction: Breast cancer (BC) is the most common malignancy in women worldwide, representing a major public health burden. Therefore, there is a need to identify circulating biomarkers for the early detection of BC and to facilitate the diagnosis. Interleukin-6 (IL-6), 4-hydroxy-2-nonenal (4-HNE), and hypoxia-inducible factor 1-α (HIF-1α) are biomarkers involved in the initiation and progression of this disease. The aim of this study was to evaluate the concentrations of these molecules and to find a possible correlation with the clinicopathological parameters of patients with BC from western Algeria. Material and methods: We evaluated the serum levels of IL-6, 4-HNE, and HIF-1α by ELISA technique and compare them in different age groups and BC molecular subtypes, and then correlated them with clinicopathological parameters. Results: Our study revealed a significant increase in 4-HNE (p < 0.05), and a negative correlation (p < 0.05) was found between IL-6 serum levels and lymph node count, but not (p > 0.05) between 4-HNE, HIF-1α and lymph node count. No significant correlation (p > 0.05) was found between IL-6, 4-HNE, HIF-1α , and Scarff-Bloom-Richardson grade. Furthermore, there was no significant difference (p > 0.05) in serum levels of IL-6, 4-HNE, and HIF-1α in the different age groups and molecular subtypes of BC. Conclusions: The data obtained show that the presence of lipid peroxidation (4-HNE) is a marker of oxidative stress, and that IL-6 is a good prognostic factor due to its negative effect on the number of lymph nodes. Furthermore, age and BC molecular subtypes do not influence the serum concentrations of IL-6,4-HNE, and HIF-1α.

Co expression of EGFR and CD10 in patients with phyllodes tumors of the breast: a single center experience in North Western Algeria.

Background: Breast phyllodes tumors (BPT) have variable malignant potential, their histological classification remains insufficient for an accurate diagnosis. Objectives: We attempted to investigate CD10 (Cluster of differentiation 10) and EGFR (Epidermal growth factor receptor) expression in BPT in order to highlight their diagnostic and prognostic values. Methods: Eight patients with BPT are recruited from January 2014 to December 2020 and immunohistochemical assessment of CD10 and EGFR is realized. Results: Median age was 27±15.2, the mean tumor size was 9.63±10.21. Only malignant tumours showed expression for EGFR. Borderline and malignant tumors were CD10 positive. Patients overexpressing CD10 were postmenopausal with great tumor size, 25% of these were sarcomatous. Coexistence of CD10 and EGFR overexpression was found in 25% of cases and was associated with age (P=0.008), tumor size (P=0.030) and hitologic types (P=0.014). PC1 and PC2, were extracted, they accounted cumulatively for 94.7% of the variance of the data analysed, it suggests that patient's age and histological type of tumor have significant association with CD10 and EGFR expression in BPT. Conclusions: EGFR and CD10 overexpressed combined proteins in phyllode tumors constitute, with histopathological parameters, an important prognostic factor as well as a promising potential targets.

Prevalence and prognosis of molecular phenotypes in breast cancer patients by age: a population-based retrospective cohort study in western Algeria.

INTRODUCTION: breast cancer is related to age. The young age remains a controversial issue as a prognostic factor and have more aggressive clinical behavior with poor outcome. We aimed for the first time in Algeria to explore on a large cohort of patients the prevalence of the molecular phenotypes and to describe their clinical characteristics and survival. METHODS: medical record of 1140 Algerian patients were analysed and categorized into three age groups: "young" when women were aged below 40 years; "middle-age" when women were aged from 41 to 54 years old and "elder" when women were over 54 years. Baseline categorical variables were analysed using the Chi-square test and survival curves were constructed using Kaplan Meir method. RESULTS: the distribution of the various prognostic factors did not differ significativelly by age groups except for histological types, hormone receptors status and molecular phenotypes. Most patients were luminal A, indeed, young and intermediate age patients were most likely to be luminal A whereas the aged patients were triple negative with the highest mean DFS. Elsewhere young women are considered as human epidermal growth factor receptor 2 (HER2+) or triple negative molecular subtypes involving more rigorous therapeutic monitoring. The high rate of triple negative breast cancer in aged patients may due to genetic predispositions. CONCLUSION: this study sheds light on the histoclinical and molecular characteristics of breast cancer in young patients, which has a good prognosis than their older counterparts. Our results are therefore surprisingly different from what the literature suggests. A further study should understand this uncommon finding.

Immunohistochemical Staining for Ras-Related Protein 25 (RAB25) Associates with Luminal B Breast Cancer Subtype.

INTRODUCTION: Luminal B breast cancer is associated with a poor prognosis and resistance to hormone therapy. Studies have suggested that Ras-related protein 25 (RAB25), a member of Rab small GTPase family, is involved in breast cancer pathogenesis. Our aim in the present study is to analyze the association between RAB25 protein expression and clinical and pathological characteristics, and to investigate whether the expression of RAB25 was associated with a specific molecular subtype of breast cancer. MATERIALS AND METHODS: A retrospective study was conducted regarding female patients diagnosed with breast cancer; clinicopathologic data was obtained from medical reports. RAB25 expression was evaluated by immunohistochemistry in 57 primary breast cancer samples. The results were correlated with clinicopathologic variables and different breast cancer molecular subtypes. RESULTS: RAB25 expression was significantly associated with tumors expressing oestrogen receptor (P=0.03). A high significant difference was observed by analyzing RAB25 expression in various breast cancer subtypes (P=0.01). RAB25 expression was found in 66.7% of Luminal B breast tumors, considered as the most aggressive hormone dependent mammary tumors and was strongly associated with luminal breast cancer subtypes (p=0.004) but not with age, tumor size, SBR grade, axillary lymph node, or tumor stage. CONCLUSION: RAB25 deregulated expression is most common in luminal B breast cancer tumors suggesting that RAB25 could be a potential therapeutic target for this molecular subtype.

[In silico study of a functional mutation associated with non-small cell lung cancer: G12D mutation of exon 2 in KRAS gene]. / Étude in silico d'une mutation : application à la mutation fonctionnelle G12D du gène KRAS, retrouvée dans les cancers bronchiques non à petites cellules.

Biology flourished during the XXth century and was profoundly disrupted during the last decade because of the transition to the post-genomic era, the spread of high-throughput biology, and the advent of a relatively new discipline, namely bioinformatics. This latter, which encompasses the collection, organization and analysis of biological data using the computer tool, has quickly become inseparable from the studies related to the genome understanding. The consequences of the different mutations that may affect our genes are responsible for a change in the protein sequence and are likely to affect, for example, the stability of the protein, its intracellular targeting, its maturation, its assembly in a multimeric structure, the essential sites for its enzymatic activity or for the interaction with ligands. Thus, a number of bioinformatic developments have made it possible to set up in silico prediction tools of the structure of a protein that is aiming at predicting the impact of local mutations on the structure of proteins. Throughout our study, we have been interested in exploring, through in silico bioinformatic study, three analytical, prediction and modeling, software, choosing as exemple the G12D mutation that affects the proto-oncogene KRAS found in numerous algerian patients with bronchopulmonary cancers cells (NSCLC). This study allowed us to integrate these bioinformatic tools into our laboratory of developmental biology and LBDD differentiation at the University of Oran 1 Ahmed Benbella, in Algeria. Thus, we have been able to conclude, even if the found mutation is predicted to be tolerated and has no deleterious effect on the entire Ras protein, that the consequence of this missense mutation depends mainly on the position in the protein and the chemical properties of the amino acid involved in the substitution and which shows a strong affinity with the GTP molecule.

[Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular profile in a population of West Algeria]. / Virus d'Epstein-Barr et carcinomes mammaires invasifs : EBNA, EBER et profil moléculaire dans une population de l'ouest algérien.

Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the clinicopathological characteristics of the population. Of the 23 cases of IDC, we implemented the techniques Elisa, immunohistochemistry and in situ hybridization. To determine the serological profile, overexpression of onco-proteins EBNA-1, HER2, the mitotic index Ki67 and detection of the presence of the viral genome. The mean age is 57.40±4, SBR II predominates with 70%, pN+ (27%), RE+ (58%), RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1 P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79 serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in the tumors 43% representing an inverse relationship with the overexpression of Ki67 and a positive relationship with the overexpression of HER2. In our study we found an association with the presence of the EBV virus and the IDC studied.

Study of Serum Carcinoembryonic Antigen's Profile for Breast Cancer in Western Algeria: 100 cases.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Biology contributes to the early diagnosis and monitoring of breast cancer with several categories of markers such as prognostic markers (ER, PR, HER2), proliferative markers (Ki67), and tumor markers such as CEA and CA 15-3. CEA can be detected at a high concentration in serum of patients with malignant tumors. AIM: The aim of our study was to evaluate the concentrations of CEA in serum of women with breast cancer and to verify the existence of a possible link between the average rates of CEA and SBR grade. METHODS: Serum samples from 100 patients with breast cancer and 100 controls was recovered and examined with an AxSYM analyzer (Abbott Laboratories, USA) to measure CEA using Microparticle Enzyme Immunoassay (MEIA) technology. RESULTS: In our clinical study, the mean age of patients and controls were 52.7 and 50.3 years respectively. The results revealed an elevation in the CEA levels from patients with an average value of 16.61 ± 0.2 ng/ml. Positive correlation was found between CEA concentrations and SBR grade, it has found with 45,7 ± 1 ng/ml in grade III. CONCLUSION: CEA represents an excellent marker for breast cancer development. Changes in its concentration reflect the effectiveness or ineffectiveness of treatment.

Assessment of hypoxic stress in 44 women with breast cancer in the West Algeria.

AIM: The objective of this study was to evaluate the expression of hypoxia-inducible transcription factor 1α (HIF1α) protein profile among women with breast cancer in a population of western Algerian and to correlate the intensity of this expression with prognosis histological grade Scarff Bloom and Richardson (SBR) of the disease and the age of the patients. METHODS: We used a kit provided by Life Science Inc (UScnk) for a sandwich enzyme immunoassay for the quantitative measurement of in vitro HIF1α in plasma in 44 patients and 44 controls in a population of western Algerian. Then we looked for the correlation between the intensity of the expression of HIF1α and prognosis histological grade SBR and the age of the patients studied. RESULTS: The results indicate high levels of HIF1α at SBRIII grade with an average value of 12.26 ± 0.5 ng/ml. The average age of patients is around 50 ± 1year. In healthy subjects the mean concentration of 1.88 ± 0.1 ng/ml represents HIF1α with a mean age of 49 ± 1year. CONCLUSION: Clinical monitoring of patients treated for breast cancer by assaying the HIF1α marker seems to be very important in the prognosis.

Retinoic acid receptor alpha and retinoid-X receptor-specific agonists synergistically target telomerase expression and induce tumor cell death.

Retinoids modulate growth and differentiation of cancer cells through activation of gene transcription via the nuclear retinoic-acid receptors (RAR) and retinoid-X receptors (RXR). Their use in differentiation therapy of acute promyelocytic leukemia (APL) represents a model concept for reprogramming cancer cells. However, they also regulate antiproliferative genes whose functions do not mechanistically concur to this program. Recently, we have shown that, independently of maturation, a long-term all-trans retinoic acid (ATRA) treatment of the maturation-resistant APL cell line (NB4-LR1) represses telomerase (hTERT), leading to telomere shortening and death. Using retinoid-receptor-specific agonists, we demonstrate herein that cross-talk between RARalpha and RXR dual-liganded to their respective agonists resulted in strong synergistic downregulation of hTERT and subsequent cell death. Importantly, unlike ATRA, this synergy was obtained at very low agonist concentrations and occurred in other ATRA maturation-resistant APL cells. These findings provide the first demonstration that dual-liganded RXR and RARalpha signaling should allow efficient targeting of telomerase in differentiation-resistant tumor cells. Such a combination therapy might hold promise in clinic to avoid side effects of ATRA whose administration can indiscriminately activate all RARs. Given the tissue-specific expression of RARs, a tissue-selective therapy targeting telomerase in tumor cells by synthetic agonists can be envisioned.