Histopathological Study of Breast Cancer at the Oran University Hospital Center on a Population from Western Algeria.

Breast cancer (BC) is the most common cancer among women worldwide and also in Algeria. Despite therapeutic progress, it remains a cancer with serious physical and psychological consequences. MATERIALS AND METHODS: The objective of this study was to perform a histological analysis on 244 patients from the western Algerian population who were receiving treatment at the Oran University Hospital. RESULTS AND DISCUSSION: The findings of our study indicates that women are more likely to be affected, with a predominance of tumors in the right breast (77%), we also found that (72%) of patients had a personal history risk of developing breast cancer. The majority of the cases that were examined were in the age range of 40 to 50. In addition, we noticed that unemployed and married women were the most affected, with (86% and 95%, respectively). Total of (63%) patients used contraceptives known to be endocrine disruptors and (68%) of cases were breast-feeding.Our results revealed that the most frequent histological type is the infiltrative ductal carcinoma (77%) followed by the ductal carcinoma in situ which is (13%), on the other hand the infiltrative lobular carcinoma presents a very low percentage (9%). The SBR II grade is the most dominant with (81%) followed by the SBRIII grade (18%) and no cases of SBR I grade were observed. CONCLUSION: Breast cancer is one of the most complex and difficult to control diseases, especially in developing countries. Breast cancer screening remains a powerful way of improving early detection and survival rate. The Findings of our study demonstrate that histopathological analysis provides an important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained for a favorable prognosis and management of breast cancer to reduce the burden of the disease. KEY WORDS: Breast cancer, risk factor, histopathology, chemotherapy and radiotherapy.

A novel mechanism of retinoic acid resistance in acute promyelocytic leukemia cells through a defective pathway in telomerase regulation.

Human telomerase, a cellular reverse transcriptase specifically activated in most malignant tumors and usually inactive in normal somatic cells, plays an important role in immortalization and tumorigenesis. Early reports have indicated that terminal differentiation of various cells is associated with a rapid inhibition of telomerase activity, preceded by a down-regulation of telomerase reverse transcriptase (hTERT) mRNA. Recently, we have shown that telomerase can be repressed by all-trans retinoic acid (ATRA) independently of terminal maturation during long-term ATRA treatment of the maturation-resistant promyelocytic leukemia cell line (NB4-R1), leading to shortening of telomeres and cell death, events overcome by ectopic hTERT expression. Here, we report the isolation of a variant of NB4-R1 cells (NB4-R1(SFD)), which bypasses this death step, because of a re-activated telomerase, despite the continuous presence of ATRA. While unresponsive to a long-term maturation independent regulation of telomerase by ATRA, these cells retain a functional pathway of telomerase down-regulation associated with retinoid-induced maturation. These findings reinforce the notion that two distinct pathways of telomerase regulation by retinoids co-exist in APL cells. Noteworthy, we show that the slow developing mechanism, that causes death of maturation-resistant cells, is subjected to a new type of retinoid-resistance as yet not understood.

All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation.

The cellular prion protein (PrPc) is a sialoglycoprotein involved in the pathogenesis of prion diseases. It has been identified at the plasma membrane of several cell types. All-trans retinoic acid (ATRA) is known to induce differentiation of human leukemia cell lines in vitro. PrPc messenger ribonucleic acid (mRNA) and protein are down-regulated upon ATRA-induced differentiation of HL60 cells. In this report, we have investigated the regulation of PrPc mRNA and protein expression during ATRA-treatment of maturation-sensitive (NB4) and -resistant (NB4-R1 and NB4-R2) cell lines. In ATRA-induced maturation of NB4 cells, down-regulation of PrPc mRNA and protein were observed. We also show that down-regulation of PrPc mRNA is dependent on protein synthesis. Moreover, the same down-regulation of prion protein by ATRA was observed at the surface of maturation-resistant, ATRA-responsive NB4-R1 cells. In contrast, the maturation-resistant and ATRA-unresponsive NB4-R2 subline showed no variation in membrane prion protein expression. These results demonstrate a dissociation between the regulation of prion protein expression by ATRA and the process of granulocyte maturation. We propose that retinoids should be investigated further as a preventive strategy to slow down prion disease progression.

The cellular prion protein: a new partner of the lectin CBP70 in the nucleus of NB4 human promyelocytic leukemia cells.

Prion diseases are characterized by the presence of an abnormal isoform of the cellular prion protein (PrPc) whose physiological role still remains elusive. To better understand the function of PrPc, it is important to identify the different subcellular localization(s) of the protein and the different partners with which it might be associated. In this context, the PrPc-lectins interactions are investigated because PrPc is a sialoglycoprotein which can react with lectins which are carbohydrate-binding proteins. We have previously characterized a nuclear lectin CBP70 able to recognize N-acetyl-beta-D-glucosamine residues in HL60 cells. Using confocal immunofluorescence, flow-cytofluorometry, and Western-blotting, we have found that PrPc is expressed in the nucleus of the NB4 human promyelocytic leukemia cell line. It was also found that the lectin CBP70 is localized in NB4 cell nuclei. Moreover, several approaches revealed that PrPc and CBP70 are colocalized in the nucleus. Immunoprecipitation experiments showed that these proteins are coprecipitated and interact via a sugar-dependent binding moiety. In conclusion, PrPc and CBP70 are colocalized in the nuclear compartment of NB4 cells and this interaction may be important to better understand the biological function and possibly the conversion process of PrPc into its pathological form (PrPsc).

Evidence for a lactose-mediated association between two nuclear carbohydrate-binding proteins.

Nuclear proteins were extracted in 2 M NaCl from membrane-depleted nuclei isolated from HL60 cells. Extracted proteins were submitted to affinity chromatography columns containing immobilized glucose, galactose or lactose. The polypeptides present in the different eluted fractions were resolved by SDS-PAGE and were either silver stained or analysed by immunoblotting with monoclonal or polyclonal antibodies, respectively, raised against the glucose-binding protein CBP67 and the galactose-binding proteins CBP35 and L14. The results presented here show that HL60 cell nuclei contain CBP35 and a glucose-binding lectin of 70 kDa (CBP70). These data account for the previously reported binding of neoglycoproteins containing glucosyl and galactosyl residues to HL60 cell nuclei. Furthermore, the present study provides the new information that CBP35 can associate with CBP70 by interactions dependent on the binding of CBP35 to lactose, and the results of some affinity chromatography experiments strongly suggest that CBP35 and CBP70 associate by protein-protein interactions. The potential function of this lactose-mediated interaction is discussed with respect to data recently reported by others showing that CBP35 is involved in in vitro mRNA splicing and that lactose inhibits the processing of the pre-RNA substrate.