A Ab bs st tr ra ac ct t Three types of calcium channels have been identified voltage-sensitive, receptor operated (cardiac muscle and vascular smooth muscle) and stretch operated (in some blood vessels) channels. Using electrophysiological and pharmacological techniques, three different types of voltage-gated calcium channels have been identified, namely, L-type (for long lasting, large channels), T-type (for transient, tiny channels) and N-type (for neuronal, neither L nor T). Many compounds are known to have a calcium channel inhibitory effect. Calcium antagonists, based on the specificity of inhibition of the slow calcium current, can be classified into three groups: Group A: for 90 to 100 percent inhibition of calcium influx without change in the sodium current (verapamil, diltiazem and the dihydropyridines); Group B: for 50 to 70 percent inhibition of calcium influx current without change in the sodium current (bepridil, cinnarizine and prenylamine) and Group C: for agents exhibiting some inhibition of calcium influx (phenytoin, indomethacin and propranolol). There is now increasing evidence that, certain calcium channel blockers especially the dihydropyridines are more strongly associated with vasodilation of afferent arterioles than of efferent arterioles and also with increase intraglomerular pressure and albuminuria. Thus they have a beneficial effect in terms of reducing proteinuria and slowing the progression of diabetic renal failure

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in Egypt and worldwide. Gene expression profiling classifies DLBCL into: germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) DLBCL. Hans' algorithm has high concordance with gene expression profiling results. Regulatory T cells (Tregs) represent important modulators for the interaction between lymphoma cells and host microenvironment. FOXP3 is a popular single marker for Tregs. There is little information about the possible role of Tregs in high-grade lymphoma such as DLBCL. This study aims to assess the prognostic impact of FOXP3+ Tregs in DLBCL. The study was carried out on 70 archival cases (61 de novo DLBCL and 9 reactive follicular hyperplasia cases). DLBCL cases were classified into GCB and non-GCB groups using Hans' algorithm. All studied cases are subjected to FOXP3 immunostaining. Density of FOXP3+ Tregs was higher in reactive cases compared with DLBCL (P=0.000). In DLBCL cases, FOXP3 expression was associated with free spleen (P=0.02), early stage (P=0.05), centroblastic variant (P=0.003), and absence of necrosis (P=0.05). In germinal cases, density of FOXP3 was significantly higher in cases with good PS (P=0.02), very good and good revised international prognostic index (P=0.002), and low-risk age-adjusted international prognostic index >60 (P=0.01). Non germinal DLBCL cases with negative FOXP3 were significantly associated with splenic involvement (P=0.005). DLBCL cases with high FOXP3 have longer survival (P=0.03). T cells in the background of DLBCL may play a role in modulation of tumor progression. Their presence is associated with favorable prognostic parameters in DLBCL.

John Cunningham virus (JCV) encodes an oncogenic T-antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirmation. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridization (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients.

Surface epithelial tumors of the ovary are no longer considered as a single disease but are divided into types I and II on the basis of their molecular features, cell of origin, and their behavior. A possible direct action of gonadal steroids on ovarian carcinogenesis has been suggested. The current information about the possible role of TFF1 in ovarian tumors,, together with its relationship to the estrogen receptor (ER) status, is insufficient. The aim of this study was to investigate ERα, ERβ, and TFF1 expression in type I and II ovarian tumors and their correlation with clinicopathologic parameters of each type. The present study was carried out on 97 ovarian tumors [20 benign, 15 borderline, and 62 malignant (36 type I and 26 type II tumors)]. ERα expression was significantly in favor of type II tumors (P=0.04), whereas high TFF1 expression was significantly in favor of type I tumors (P=0.02). ERα and ERβ showed a significant positive correlation in benign cases (P=0.004) and in type I tumors (P=0.006), but not in type II tumors. In type I tumors, the expression of ERα was correlated with serous carcinoma (P=0.002) and bilaterality (P=0.05), whereas TFF1 was correlated with mucinous carcinoma (P=0.02), unilaterality (P=0.04), early FIGO staging (P=0.01), and a low mitotic count (P=0.03). A high ERβ:ERα H score ratio was associated with advanced FIGO staging in both type I (P=0.05) and type II tumors (P=0.009). The difference in the expression of ERα and TFF1 between type I and II tumors may be indicative of the difference in their origin and molecular pathway. The ERβ:ERα ratio is more important in determining the net result of ER effects than the evaluation of each receptor separately, and the high ratio may promote progression to advanced stage in type I and II ovarian tumors. High TFF1 expression in ovarian mucinous carcinoma may indicate that their mucinous differentiation is toward an intestinal type rather than an endocervical type. TFF1 expression in ovarian tumors seems to occur independent of the status of the ER.

Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and it is highly expressed in various cancers. Therefore, inhibition of CAIX is considered as a promising therapeutic target for the treatment of solid tumors where hypoxic environment has developed. The aim of the current work is to evaluate the immunohistochemical (IHC) expression of CAIX in breast cancer (BC) of Egyptian patients and to investigate the associations of CAIX expression with the standard clinicopathologic features, IHC subtypes of BC, and overall survival. This retrospective study was conducted on 56 archival cases of Egyptian BC patients. Fifty-one of 56 cases (91.1%) showed positive expression of CAIX with cytoplasmic localization, whereas 5 cases (8.9%) showed negative expression. CAIX IHC overexpression is significantly associated with advanced stage and presence of coagulative tumor cell necrosis (P=0.03 and 0.02, respectively). Multivariate analysis revealed Ki67 labeling index and CAIX H-score grouping (P=0.03 and 0.02, respectively) as independent prognostic factors affecting BC patients' overall survival. We concluded that CAIX could play a role in the progression of the studied BC cases. CAIX is a good candidate for target therapy.