FSH receptor binding inhibitor up-regulates ARID1A and PTEN genes associated with ovarian cancers in mice

Experiments were conducted to determine if the follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI) impacts the expression levels of AT-rich interactive domain-containing protein 1A (ARID1A) and phosphatase and tensin homolog (PTEN) in ovaries and blood, as well as expressions of follicle-stimulating hormone cognate receptor (FSHR) gene and proteins. Mice in FRBI-10, FRBI-20, FRBI-30, and FRBI-40 groups were intramuscularly injected with 10, 20, 30, and 40 mg FRBI/kg, respectively, for five consecutive days. Western blotting and qRT-PCR were utilized to determine expression levels of ARID1A and PTEN proteins and mRNAs. Serum ARID1A and PTEN concentrations of the FRBI-40 group were higher than the control group (CG) and FSH group (P<0.05). FSHR mRNA levels of FRBI-20, FRBI-30, and FRBI-40 groups were lower than that of CG and FSH groups on day 15 (P<0.05 or P<0.01). Expression levels of FSHR proteins of FRBI-30 and FRBI-40 groups were lower than those of CG and FSH groups (P<0.05). Levels of ARID1A and PTEN proteins of the FRBI-30 group were greater than CG on days 20 and 30 (P<0.05). FRBI doses had significant positive correlations to levels of ARID1A and PTEN proteins. Additionally, ARID1A and PTEN had negative correlations to FSHR mRNAs and proteins. A high dose of FRBI could promote the expression levels of ARID1A and PTEN proteins in ovarian tissues. FRBI increased serum concentrations of ARID1A and PTEN. However, FRBI depressed expression levels of FSHR mRNAs and proteins in mouse ovaries.

Cytoplasmic nucleophosmin [cNPM] in acute myeloid leukaemia: Relation to disease characteristics

Nucleophosmin/B23 [NPM] is a 38 kDa molecular phosphoprotein involved in ribosome assembly and transport. Findings have revealed a complex scenario of NPM functions and interactions, pointing to proliferative and growth-suppressive roles. NPM appears to be more abundant in tumour cells than in normal cells. The aim of the work was to identify cytoplasmic localization of NPM using bone marrow clot biopsy and correlate it with disease and patient characteristics and the known prognostic factors, induction chemotherapy response and survival after 12 months of follow up. The present work was undertaken on 50 cases of normal karyotype acute myeloid leukaemia classified according to modified FAB system. Bone marrow aspirates were obtained, clotted and a formalin-fixed, paraffin embedded cell block was prepared. Sections were immunostained for NPM. Twenty-six cases [52%] had cytoplasmic positivity [cNPM+] while the remaining 24 cases [48%] had nuclear restricted NPM [cNPM]. cNPM positivity was significantly variable among the different FAB subtypes being the most prevalent among M5 and M2 cases, was associated with high blast and white blood cell count at diagnosis. It was significantly correlated with CD34 negativity, CD14 positivity but not with FLT3 mutations. Clinically no relation between cNPM positivity and age, sex nor extramedullary involvement of the studied patients was proven. The cytoplasmic positivity for NPM was significantly correlated with increased survival and better outcome after cycles of chemotherapy. So it can be regarded as a good prognostic marker. FLT3 positivity affected the survival of the cNPM negative group of patients remarkably, denoting the importance of combining both their statuses to predict outcome of therapy and survival. Our data confirm that cytoplasmic NPM1 immunoreactivity is predictive of NPM1 mutations and can be included in the routine diagnostic and prognostic workup of AML

Angiotensinogen gene [M235T] variant and pre-eclampsia in Egyptian pregnant women

Association between the angiotensinogen gene [M235T] and pre-eclampsia has been confirmed in recent studies. Pre-eclampsia is a complication of pregnancy characterized by increased vascular resistance, higher blood pressure, proteinuria and oedema that appear in the second and third trimester of pregnancy. This study aimed at investigating the relationship between M235T gene polymorphism and pregnant women with different forms of pre-eclampsia. One hundred and fifteen pre-eclamptic women and 100 normal control group were recruited and evaluated for the frequency of M235T mutation using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. A positive association was found between maternal age over 35 years [OR = 6.67; CI: 2.09-23.59], previous family history of hypertension [OR = 3.01; CI: 1.18-7.66], previous pre-eclampsia [OR = 7.44; CI: 2.47-22.42], history of reproductive losses [OR = 53.98; CI: 3.23-90.88], fetal anomalies [OR = 8.4; CI: 1.06-180.33], and pre-eclampsia. The frequency of heterozygous carriers of M235T mutation in pre-eclampsia [19.1%] was higher than that in control [14%] but the difference was statistically non-significant. Also, the frequency of M235T mutation was higher in mild pre-eclampsia women [63.6%] compared to women with severe pre-eclampsia [36.4%], however this was statistically non-significant. This study revealed that the frequency of M235T mutation was higher within women with mild pre-eclampsia