Detailed Profiling of the Tumor Microenvironment in Ethnic Breast Cancer, Using Tissue Microarrays and Multiplex Immunofluorescence.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

Aberrant expression of cell cycle regulatory genes predicts overall and disease free survival in malignant pleural mesothelioma patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM. PATIENTS AND METHODS: Aberrant expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&DFS). RESULTS: Altered expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1) and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53, p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03, p=0.01). CONCLUSIONS: MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only p27(KIP1)and Rb could be used as molecular prognostic markers in MPM.

Clinical, Histopathologic Features and Outcome of Breast Cancer in UK Women of Ethnic Origin.

OBJECTIVE: Breast cancer (BC) in non-Caucasian females is understudied and its management is based on Caucasian data. 30 % of the West Midlands females are non-Caucasian. We aimed to elucidate the pathologic features, molecular profile, and outcome of non-Caucasian breast cancer. METHODS: Breast cancers (BCs) of different ethnic origins diagnosed at a large Birmingham tertiary referral hospital between 2000 and 2016 were identified. Detailed clinical and histological data were collected and statistically analyzed. RESULTS: Out of 7554 BC cases, 749 were of ethnic ancestry and median age of 51 years. These comprised 47 in-situ and 702 invasive carcinomas of presenting symptomatically in 86.2% of patients. 53.4% of the invasive carcinomas measured >20 mm. Cancers were predominantly of grade 3 (45%), and grade 2 (42.4%). Median NPI was 4.35. 65.1% of the ethnic carcinomas were of luminal subtype, 18.6% were Her2 positive and 16.2% triple-negative. Median overall survival was 62 months. Five and ten-year survival was 81.7% & 68.4% respectively. Ethnicity correlated with higher NPI (p <0.001), larger tumour size (p= 0.001) and larger number of positive axillary nodes (p=0.007). Negative correlations were found between age at diagnosis and both invasive tumour size & grade (p< 0.001) and between tumour grade and overall survival (p= 0.006). CONCLUSION: Compared with Caucasian breast cancer, non-Caucasian tumours presented predominantly symptomatically at younger age, were of larger size, higher grade with more unfavorable phenotypes and shorter survival. This is important in counselling, planning management and follow up of non-Caucasian patients.

Effect of Ce-doped bioactive glass/collagen/chitosan nanocomposite scaffolds on the cell morphology and proliferation of rabbit's bone marrow mesenchymal stem cells-derived osteogenic cells.

BACKGROUND: Cerium-containing materials have wide applications in the biomedical field, because of the mimetic catalytic activities of cerium. The study aims to deeply estimate the biocompatibility of different scaffolds based on Ce-doped nanobioactive glass, collagen, and chitosan using the first passage of rabbit bone marrow mesenchymal stem cells (BM-MSCs) directed to osteogenic lineage by direct and indirect approach. One percentage of glass filler was used (30 wt. %) in the scaffold, while the percentage of CeO2 in the glass was ranged from 0 to 10 mol. %. Cytotoxicity was evaluated by monitoring of cell morphological changes and reduction in cell proliferation activity of BMMSCs maintained under osteogenic condition using proliferation assays, MTT assay for the direct contact of cells/scaffolds twice in a week, trypan blue and hemocytometer cell counting for indirect contact of cells/scaffolds extracts at day 7. Cell behaviors growth, morphology characteristics were monitored daily under a microscope and cell counting were conducted after 1 week of the incubation of the cells with the extracts of the four composite scaffolds in the osteogenic medium at the end of the week. RESULTS: Showed that at 24 h after direct contact with composite scaffold, all scaffolds showed proliferation of cells > 50% and increased in cell density on day 7. The scaffold of the highest percentage of CeO2 in bioactive glass nanoparticles (sample CL/CH/C10) showed the lowest inhibition of cell proliferation (< 25%) at day 7. Moreover, the indirect cell viability test showed that all extracts from the four composite scaffolds did not demonstrate a toxic effect on the cells (inhibition value < 25%). CONCLUSION: The addition of CeO2 to the glass composition improved the biocompatibility of the composite scaffold for the proliferation of rabbit bone marrow mesenchymal stem cells directed to osteogenic lineage.

In Vitro Biological Evaluation of a Fabricated Polycaprolactone/Pomegranate Electrospun Scaffold for Bone Regeneration.

Different scaffold biomaterials are being investigated as a solution for bone loss due to disease or trauma. The aim of this study is the fabrication, characterization, and in vitro biological evaluation of a novel polycaprolactone (PCL) nanoscaffold incorporating pomegranate peel extract (PG) for bone regeneration. Using electrospinning, three groups of scaffolds were prepared: the control group PCL and two groups of PCL with PG concentrations (11 and 18 weight %). The antioxidant activity and the total phenolic content (TPC) of the fabricated nanoscaffolds were evaluated, in addition to the porosity and degradation measurement. Cultured osteoblasts derived from rabbit bone marrow mesenchymal stem cells were used for the assessment of cell proliferation and attachment on the scaffold's surface. Scaffolds' characterization showed uniform nanofibers (NFs) with a fiber diameter range of 149-168 nm. Meanwhile, higher antioxidant activity and TPC of the PG groups were detected. Furthermore, total porosities of 59 and 62% were determined for the PCL-PG scaffolds. An increased degradation rate and significant improvement in cell proliferation and cell attachment were revealed for the PCL-PG fabricated scaffolds. Such incorporation of natural food waste, PG, in PCL NFs offered novel PCL-PG scaffolds as a promising candidate for bone regeneration applications.

Green carboxymethyl cellulose-silver complex versus cellulose origins in biological activity applications.

This article deals with evaluating the role of cellulose origin, from wood and non-wood, on preparing green CMC-Ag complex as biological active agent. Viscose pulp as well as bagasse and rice straw pulps were used in preparation of CMCs, followed by complexation with AgNO3. The complex structure (free-Ag, IR-spectra and TGA), morphology (TEM), antibiological and anti-tumor activities were studied. The data revealed that, the main interaction between CMC and silver is occurred via carboxylate groups and ether link of 1ry alcohol, with formation stable 5-membered ring structure. For the case of RS-based CMC-Ag complex the interaction between COO groups and silica included RS is also possible, via hydrogen bonds. These complexes have anti-biological especially towards gram positive bacteria (B.subtilis, NCID-3610), and uni- and multi cellular fungi. AgNPs from viscose (VCMC-Ag complex) has relatively higher anti-tumor activity for breast cancer MCF-7 in vitro than bagasse-based CMC-Ag complex (BCMC-Ag complex) with IC50 128µg/ml (as Ag). It is interesting to note that; viscose-based CMC-Ag complex (VCMC-Ag) has higher efficient behaviour as bioactive agent than literature reported agents, e.g., Pyridine derivative (∼300µg/ml).

Properties of modified carboxymethyl cellulose and its use as bioactive compound.

The present study deals with synthesizing novel cellulose derivative, from modifying the carboxymethyl cellulose with amino phenylpropanoic acid (CMC-APP). The synthesized CMC-APP was evaluated as biological and anti-cancer active compound. The molecular structures of this active compound were built using the HyperChem program 7.5, together with conventional analysis (nitrogen content, FT-IR, and non-isothermal TGA analysis). Optimizing the CMC/APPA ratio was carried out as preliminary assessment step, via undetected antimicrobial activity measurement. The TEM study showed that, the synthesized cellulose CMC-APP derivative in the nano-scale particle size (range from 12.5 to 89.3nm). Among all the tested microorganisms and MCF-7 breast cancer cells, the synthesized nano-cellulose derivative is possible used as safety medicine for microbial infections and cancers. The minimal inhibitory concentration (MIC) for Gram-positive bacteria, and gram-negative bacteria are 48.82µg/mL and 97µg/mL, respectively. While, the unicellular fungi and filamentous fungi are 12.2µg/mL and 97.65µg/mL, respectively. The cytotoxic index (IC50) for MCF-7 breast cancers is 50µg/mL. Moreover, the computational study of ADMET (absorption, distribution, metabolism, elimination and toxic) properties, of the molecules showed that, this investigated nano-compound is good oral bioavailability.

Cyclooxygenase-2 expression is associated with elevated aspartate aminotransferase level in hepatocellular carcinoma.

BACKGROUND: Cyclooxygenase-2 (COX-2), the inducible rate-limiting enzyme of prostaglandins biosynthesis, is involved in the pathogenesis of many chronic inflammation-related human malignancies including hepatocellular carcinoma (HCC). However, its clinical significance in HCC remains obscure. The aim of our study was to evaluate COX-2 expression in HCC and correlate its expression to both clinicopathological parameters and patients survival. MATERIALS AND METHODS: The present study was conducted on 17 HCC and 21 adjacent nontumor liver tissues obtained from 22 HCC patients underwent hepatectomy. Eight normal liver tissues taken from normal donors and HepG2 cells were used as controls. Total RNA was extracted and COX-2 mRNA was detected by reverse transcription polymerase chain reaction and correlated to the clinicopathological criteria and to patient's survival. RESULTS: COX-2 mRNA was detected in 58.8% of the HCC tissues and in 28.6% of the adjacent nontumor liver tissues. COX-2 expression was significantly associated with elevated levels of serum aspartate aminotransferase (AST) with high specificity for disease detection. There was no significance between COX-2 expression and any of the histopathological criteria. CONCLUSIONS: COX-2 expression may be involved in HCC carcinogenesis with high specificity for disease detection. COX-2 expression is significantly associated with elevated AST levels indicating a mechanism that may correlate both markers. However COX-2 expression seems to be an independent factor with no correlation to any of the histopathological data or patient's survival.