ABO blood groups in relation to breast carcinoma incidence and associated prognostic factors in Moroccan women.

The association between blood groups ABO and different types of diseases was established in several previous studies. Our aim was to seek the possible association between the ABO blood group and breast cancer-associated prognostic factors. The Chi-squared analytic test was used to compare phenotypic ABO distribution among Moroccan blood donors and 442 cases of women suffering from breast carcinoma with archived files in Maternity Ward of University Hospital C.H.U Ibn Rochd between 2008 and 2011. High incidence of breast carcinoma was observed in blood type B patients (p < 0.05). Blood type B was associated with breast carcinomas overexpressing human epidermal growth factor receptor HER2 (p < 0.05) and high risk of cancer at age over 70 years (p < 0.001). Blood type A was associated with high risk of cancer among women younger than 35 years old. Blood type A and AB were associated with high incidence of lymph node metastasis (p < 0.05). Multivariate analysis has shown correlation between O blood type and estrogen receptor-positive tumor. Patients with blood group A, B, and AB were more likely to develop aggressive breast carcinoma. Further follow-up studies are necessary to clarify the role of ABH antigens in the progression of breast carcinoma.

Immunohistochemical expression of latent membrane protein 1 (LMP1) and p53 in nasopharyngeal carcinoma: Moroccan experience.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor intimately associated with Epstein-Barr virus (EBV). NPC is a characteristic tumor displaying epidemiological, genetic and regional distribution properties that makes it unique by its natural behavior. OBJECTIVES: To assess the expression pattern of LMP1 and p53 proteins in the different histological types of NPC in a sample of the Moroccan population and to define any association between the expression of those proteins with the sex, the age and the histological types of NPC. METHODS: Archival formalin-fixed, paraffin-embedded NPC biopsies were evaluated in 23 Moroccan patients for the presence of LMP1 and p53 using immunohistochemistry (IHC). RESULTS: No LMP1 expression was observed whereas 8 of 23 cases (34. 7%) had detectable p53 protein in the nuclei of tumor cells. After statistical analysis according to the Fisher's exact probability test, no significant association between p53 expression and histological type, age and sex distributions was demonstrated (p>0.05). CONCLUSION: This study confirms that p53 overexpression is present in a subset of Moroccan NPC patients. Our results are consistent with those reported by other studies concerning the same NPC endemic risk area and provide original data concerning Morocco.

Colorectal cancer: comparison of clinicopathologic features between Moroccans patients less than 50 years old and older.

INTRODUCTION: Colorectal cancer is a major public health problem. However, this cancer is usually developed on preexisting lesion. This makes this cancer accessible to a prevention strategy. OBJECTIVE: The aim of this study was to determine the clinicopathologic characteristics of patients under 50 years. PATIENTS AND METHODS: This study involved 133 patients with colorectal cancer recruited in CHU Ibn-Rochd, Casablanca. Data relating age, sex, stage at presentation, histological type and tumor location were obtained from the pathological and clinical records of each patient. Statistical analysis was performed to compare clinicopathological data in patients under 50 years and in older patients. RESULTS AND DISCUSSION: The average age of patients was 54 years. The frequency of patients aged 50 or under was 40.6% The tumors in the youngest age group were more often mucinous and signet ring cells (18.5%) versus (5.1%) in the oldest age group. The right colon was more often affected in the youngest age group, 38.9% versus 17.7% in the oldest age group (P=0.008). CONCLUSION: The proposition of colorectal cancer in subjects 50 or under was high in Morocco. Colorectal cancers in the youngest age group were more often mucinous or signet ring cells and was more often located in the right colon. We intend to complete this study by a genetic study to help improve prevention and care of young patient.

Characterization of a membrane tyrosine phosphatase in AR42J cells: regulation by somatostatin.

A phosphotyrosyl protein phosphatase (PTPase) activity has been characterized in the plasma membranes of confluent AR42J pancreatic tumor cells using 32P-labeled poly(Glu, Tyr) as substrate. Membrane PTPase activity exhibited an apparent Michaelis constant of 3 microM and an apparent maximal velocity of 0.9 nmol.min-1.mg-1. It was inhibited by orthovanadate, zinc, poly(Glu,Tyr) and was stimulated by EDTA and dithiothreitol. Gel filtration of solubilized plasma membranes gave a peak of enzyme activity at a relative molecular weight of 70,000. Plasma membrane PTPase activity was changed during AR42J cell growth. At the beginning of culture, the control PTPase activity was minimal. Over the 5 days of culture, PTPase activity increased to reach a maximum (3.5-fold over control activity) preceding confluency by 2 days. Then the high level of PTPase activity was sustained until confluency. Incubation of the cells with the stable somatostatin analogue SMS 201-995 (SMS) resulted in a rapid and transient activation of crude membrane PTPase activity. Activation reached a maximum level within 5 min of addition and return to control levels within 20 min. The effect of SMS was dose dependent with half-maximal and maximal activation occurring at 6 pM and 0.1 nM SMS respectively.

Basic fibroblast growth factor induces proliferation of a rat pancreatic cancer cell line. Inhibition by somatostatin.

AR4-2J, a rat pancreatic acinar-tumor cell line, was used to investigate long-term effects of basic fibroblast growth factor (bFGF) and somatostatin on pancreatic cancer cells. We observed that bFGF stimulated cell proliferation when cells were cultured in serum-free medium. The effect was dose-dependent with half-maximal and maximal effects at 25 pM and I nM bFGF, respectively. The somatostatin analog SMS 201-995 (SMS) decreased the growth-promoting effect of bFGF. The maximal effect was observed at I nM SMS and the half-maximal effect at 20 pM SMS. Characterization of bFGF receptor-binding properties with [125I]bFGF revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/10(6) cells. High-affinity receptors correlated with bFGF stimulation of AR4-2J cell growth, suggesting that the effects of bFGF are receptor-mediated.

Somatostatin 28 interacts with CCK receptor in brain and pancreas.

The ability of somatostatin analogs to interact with the binding of cholecystokinin has been studied in pancreatic and brain cortical membranes. Only the 28 amino-acid forms of somatostatin (S28), [Nle8]S28 and [Des Lys14,DTrp22]S28 were found to inhibit the binding of cholecystokinin to rat pancreatic plasma membranes and to increase the amylase release from pancreatic acini. This effect was independent of somatostatin receptor and resulted from an interaction between S28 and CCK receptor. This interaction was not observed with [Leu8, DTrp22, Tyr25]S28, indicating that this analog does not possess the biological activity of the native peptide and that the iodinated peptide could not label specific S28 receptors. S28 interacted also with CCK receptors in cortical brain membranes. Our results support the concept that S28, but not S14, may function as a regulatory molecule at CCK receptors and emphasize that S28 and S14 may be distinct neuromodulators.

Regulation of proliferation by fibroblast growth factor in a pancreatic cancer cell line.

Basic fibroblast growth factor (bFGF) is a potent mitogen for various cell types. We report here the first study of the effects of bFGF on a digestive tract-derived cell line. The effect of bFGF on the proliferation of AR4-2J cells, tumor cells of acinar pancreatic origin, was investigated together with modulation of ornithine decarboxylase (ODC) activity, an intracellular event involved in cell proliferation. bFGF caused a concentration-dependent stimulation of AR4-2J cell growth, with a half maximal effect (EC50) at 22 +/- 2 pM. ODC activity, assayed by the CO2-trapping method, was also increased by bFGF in a dose-dependent manner, reaching half-maximal stimulation at 20 pM. We conclude that bFGF is a very potent growth promoting factor for cells of pancreatic origin, already effective at picomolar concentrations. The parallelism between the growth assay and the ODC activity assay implicates the involvement of ODC activity in the pathway of the mitogenic effect of bFGF. The stimulation of ODC activity therefore seems to be a reliable early marker for cell proliferation in this model.

Direct inhibitory effects of a somatostatin analog, SMS 201-995, on AR4-2J cell proliferation via pertussis toxin-sensitive guanosine triphosphate-binding protein-independent mechanism.

Somatostatin has been demonstrated to negatively regulate pancreatic growth in vivo. In this study we used the AR4-2J rat pancreatic acinar tumor cell line to investigate the effect of a stable somatostatin analog, SMS 201-995 (SMS) on cell proliferation. SMS induced an antiproliferative effect on both serum or epidermal growth factor (EGF)-induced cell proliferation; exposure of the cells for 48 h to SMS caused a slight inhibition of serum-induced proliferation (maximal inhibition, 26%) and abolished the growth-promoting effect of EGF. Maximal effect was observed with 10 nM SMS, and half-maximal (IC50) effect with 0.06-0.1 nM SMS. Binding studies with an iodinated derivative of SMS, [125I-Tyr3]SMS, revealed the presence of a single class of high affinity binding sites on AR4-2J plasma membranes with an equilibrium dissociation constant of 0.2 +/- 0.03 nM and a binding site number of 1.1 +/- 0.07 pmol/mg protein. Addition of the nonhydrolyzable GTP analog, guanosine 5-[gamma-thio] triphosphate (GTP gamma S), increased the rate of dissociation of the specifically bound peptide in agreement with the coupling of somatostatin receptors with a GTP-binding regulatory protein. The good agreement between the IC50 for SMS inhibition of cell proliferation and the apparent Kd for binding indicates that the characterized binding sites are the somatostatin receptors that mediate the antiproliferative effect of SMS. When cells were grown in serum-free medium EGF stimulated AR4-2J cell proliferation with half-maximal (ED50) and maximal effects at 0.6 and 10 nM EGF, respectively. This stimulatory effect of EGF was mediated by specific receptors, since binding studies with [125I]EGF indicated that AR4-2J cells contained a single class of EGF receptors (13,000 sites/cell), with an affinity constant for [125I]EGF (Kd = 0.9 +/- 0.09 nM) close to the ED50 for EGF stimulation of cell growth. To examine if SMS-induced growth inhibition involved a cAMP-dependent mechanism we first studied the effect of SMS on cAMP production. SMS had no effect on basal cAMP, but completely inhibited VIP-stimulated cAMP production with an IC50 of 0.2 nM. Pertussis toxin, which is known to abolish the inhibitory effect of somatostatin on adenylate cyclase activity in AR4-2J cells, did not reverse the ability of SMS to inhibit cell proliferation as well as EGF-induced cell proliferation. These data indicate that the antiproliferative effect of SMS does not involve the GTP-binding protein-mediated negative coupling of somatostatin receptors to adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional somatostatin receptors on a rat pancreatic acinar cell line.

Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125I-[Tyr11]somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites (Kd = 0.55 +/- 0.06 nM) with a maximal binding capacity of 258 +/- 20 fmol/10(6) cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125I-[Tyr11]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide (Mr 80,000) containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation (IC50 = 0.4 nM) was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. We conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein Ni to inhibit adenylate cyclase.