New nano-complexes targeting protein 3S7S in breast cancer and protein 4OO6 in liver cancer investigated in cell line.

Cancer, a lethal ailment, possesses a multitude of therapeutic alternatives to combat its presence, metal complexes have emerged as significant classes of medicinal compounds, exhibiting considerable biological efficacy, especially as anticancer agents. The utilization of cis-platin in the treatment of various cancer types, including breast cancer, has served as inspiration to devise novel nanostructured metal complexes for breast cancer therapy. Notably, homo- and hetero-octahedral bimetallic complexes of an innovative multifunctional ether ligand (comprising Mn(II), Ni(II), Cu(II), Zn(II), Hg(II), and Ag(I) ions) have been synthesized. To ascertain their structural characteristics, elemental and spectral analyses, encompassing IR, UV-Vis, 1H-NMR, mass and electron spin resonance (ESR) spectra, magnetic moments, molar conductance, thermal analysis, and electron microscopy, were employed. The molar conductance of these complexes in DMF demonstrated a non-electrolytic nature. Nanostructured forms of the complexes were identified through electron microscopic data. At ambient temperature, the ESR spectra of the solid complexes exhibited anisotropic and isotropic variants, indicative of covalent bonding. The ligand and several of its metal complexes were subjected to cytotoxicity testing against breast cancer protein 3S7S and liver cancer protein 4OO6, with the Ag(I) complex (7) evincing the most potent effect, followed by the Cu(II) with ligand (complex (2)), Cis-platin, the ligand itself, and the Cu(II)/Zn(II) complex (8). Molecular docking data unveiled the inhibitory order of several complexes.

Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. METHODS: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. RESULTS: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. CONCLUSION: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

Intratumoral FOXP3+ Regulatory T Cells in Diffuse Large B-Cell Lymphoma.

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.

Overexpression of Carbonic Anhydrase IX is a Dismal Prognostic Marker in Breast Carcinoma in Egyptian Patients.

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.

Immunohistochemical expression of ERα, ERß, and TFF1 in type I and II ovarian tumors.

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, ERß, 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 ERß 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 ERß: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 ERß: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.

Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma?

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.

Cyclooxygenase-2 expression in chronic gastritis and gastric carcinoma, correlation with prognostic parameters.

BACKGROUND: Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in numerous processes such as cellular growth, differentiation, inflammation and tumorogenesis. PURPOSE: Assessment of Cox-2 expression in chronic gastritis and gastric carcinoma. MATERIAL AND METHODS: Sixteen chronic gastritis (CG) and 43 gastric carcinoma cases were subjected to an immunohistochemical approach using anti Cox-2 antibody. RESULTS: All CG cases displayed positive epithelial Cox-2 expression with only 25% positivity for stromal expression. Eighty six percent of gastric carcinoma showed epithelial Cox-2 expression that was significantly correlated with lymph node involvement (p<0.01), advanced stage (p=0.01), high microvessel density (MVD) (p=0.0001), vascular invasion (p=0.002), perineural invasion (p=0.01) and low apoptotic count (p<0.0001). Stromal Cox-2 expression was seen in 79% of gastric carcinoma cases and was significantly associated with low apoptotic count (p=0.0007), vascular invasion (p=0.001) and high microvessel density (MVD) (p=0.0003). Only stromal Cox-2 expression was significantly higher in gastric carcinoma than chronic gastritis (p=0.0001). CONCLUSIONS: Cox-2 appears to be involved in gastric carcinoma progression as it promotes angiogenesis, suppresses apoptosis and facilitates invasion and metastasis. Double expression of Cox-2 in gastric carcinoma epithelium and stroma and significant association between them demonstrate a paracrine cross effect between stromal and malignant epithelium.

Human telomerase reverse transcriptase (hTERT) gene expression in thyroid carcinoma: diagnostic and prognostic role.

BACKGROUND: The catalytic component of telomerase, human telomerase reverse transcriptase (hTERT) has been found to be reactivated in immortalized cell lines and considered as a diagnostic marker for malignancy in different body tissues. AIM OF WORK: Therefore we thought to determine whether hTERT gene detection could serve as an adjunct in the diagnosis of thyroid lesions together with evaluation of its prognostic value. PATIENTS AND METHODS: The study included 50 cases of primary thyroid carcinoma including; 28 papillary carcinoma, 14 follicular carcinoma, 5 anaplastic carcinoma and 3 medullary carcinoma in addition to 5 cases of nodular hyperplasia and 5 cases of follicular adenoma. RNA was extracted from paraffin sections of those patients and hTERT gene expression was identified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). RESULTS: RT-PCR of hTERT gene revealed expression in 43/50 (86%) malignant thyroid cases; including 25 papillary, 11 follicular, 4 anaplastic and 3 medullary carcinoma cases. On the other hand, hTERT gene expression could not be detected in either hyperplastic nodule or in follicular adenoma cases. The diagnostic validity of hTERT gene detection in benign and malignant thyroid lesions was in the form of 88.3% accuracy, 86% sensitivity, 100% specificity, 100% positive predictive value and 90% negative predictive value. No significant association has been found between hTERT gene expression and any clinicopathologic parameters concerned in this study. In thyroid carcinoma cases, hTERT gene detection was the most independent predictor of poor survival by multivariate survival analysis. CONCLUSION: Detection of hTERT gene expression should be considered in confirmation of malignant thyroid lesions. Moreover it could be one of the helpful tools in addition to grade, tumor type, and age to stratify patients with thyroid carcinoma into different prognostic categories. Hence, inhibition of hTERT could be of use prospectively in the era of cancer therapy as an attractive weapon in thyroid carcinoma.