Mehdi Haghi

Background: Colon cancer remains a major global health concern, and conventional chemotherapy is often associated with systemic toxicity and therapeutic resistance. Nanocarrier-based drug delivery systems are being investigated as potential approaches to improve the delivery of anticancer agents. Objectives: This study aimed to develop magnetic bovine serum albumin nanoparticles co-loaded with curcumin (CUR) and paclitaxel (PTX) and to evaluate their physicochemical characteristics and in vitro cytotoxic effects against Ls174T colorectal cancer cells. This formulation combines the drug-carrying properties of BSA with the magnetic responsiveness of cobalt ferrite (CoFe2O4); however, magnetic field-guided targeting was not evaluated. Methods: Nanoparticles were prepared using the desolvation method with incorporation of a CoFe2O4 magnetic core. Their physicochemical characteristics were evaluated using scanning electron microscopy and Fourier-transform infrared spectroscopy. Cytotoxicity was assessed using methylthiazolyl tetrazolium assays in Ls174T human colorectal cancer cells after 24, 48, and 72 h of treatment. Results: The dual-loaded nanoparticles exhibited greater in vitro cytotoxic activity against Ls174T cells than did the corresponding single-drug formulations and free drugs under the tested conditions. Curcumin alone showed relatively limited cytotoxic activity, whereas its combination with paclitaxel was associated with enhanced cytotoxic effects. These findings demonstrate the in vitro activity of the dual-loaded formulation; however, its effects on systemic toxicity and tumor-specific targeting remain undetermined. Conclusions: bovine serum albumin-CoFe2O4 nanoparticles co-loaded with CUR and PTX demonstrated in vitro cytotoxic activity against Ls174T colorectal cancer cells. These findings support further investigation of this formulation as a potential platform for combined anticancer drug delivery. Additional studies using normal cell models and in vivo tumor models are required to evaluate cytotoxic selectivity, biodistribution, tumor targeting, systemic toxicity, and therapeutic efficacy.

Background: Prostate cancer (PCa) is genetically a complicated disease with mediation by variations in genes coding for androgen biosynthesis and signaling genes. In the current study, we investigate the associations of key polymorphisms in the androgen pathway with serum testosterone and prostate-specific antigen (PSA) levels, while also exploring their potential functional impact using bioinformatics analyses. Methods: A total of 314 patients with prostate adenocarcinoma and 287 age-matched healthy controls were genotyped for ten SNPs across CYP17A1, HSD3B1, HSD3B2, SRD5A2, and AR genes using sequencing methods. Associations with disease risk, serum testosterone, and PSA were evaluated. Functional predictions, linkage disequilibrium (LD), and protein–protein interaction (PPI) network analyses were performed in silico . Results: Significant associations were found for CYP17A1 (rs10883783), HSD3B1 (rs6203, rs33937873), SRD5A2 (rs12470143) with PCa risk, whereas androgen receptors polymorphisms (rs1204038, rs6152) and HSD3B2 (rs1819698, rs58154933) showed no association. The A allele of CYP17A1 rs10883783 and the T allele of HSD3B1 rs6203 were correlated with lower testosterone levels, while only the CYP17A1 rs10883783 polymorphism was significantly associated with increased PSA levels. Bioinformatic analysis showed potential deleterious effects for the HSD3B1 rs6203 variant, as well as regulatory effects for CYP17A1 rs10883783, in accordance with their corresponding enzymatic role in androgen biosynthesis. Additionally, analysis of PPI and co-expression networks revealed tight functional connectivity of the androgen pathway genes. Conclusion: These results suggest a biological function for genetic polymorphisms of HSD3B1 and CYP17A1 in PCa susceptibility and androgen regulation. These polymorphic variants can serve as effective risk biomarkers for PCa and disease activity using a combination of genotyping, hormone assay, and bioinformatics. These findings need more research, including larger multi-ethnic cohorts and functional validation to ascertain their therapeutic relevance.

Breast cancer (BC) is a complex genetic disorder and a major global health concern among women. The rising incidence of BC highlights the need for reliable molecular biomarkers to enable early diagnosis, monitor disease progression, and guide therapeutic interventions. MicroRNAs (miRNAs) have emerged as promising candidates due to their key regulatory roles in gene expression and their diagnostic and prognostic potential. In this study, serum miR-9-5p expression was evaluated in 100 BC patients and 100 healthy controls using quantitative real-time PCR (qPCR). Potential target genes of hsa-miR-9-5p were predicted using the miRDB database and ranked according to interaction scores. Serum miR-9-5p was significantly upregulated in BC patients compared with healthy controls (P-value < 0.0001). The marked elevation of serum miR-9-5p in BC patients suggests its possibility potential as a non-invasive biomarker for early detection. The predicted target genes warrant further functional validation to clarify the molecular mechanisms underlying hsa-miR-9-5p-mediated regulation in breast cancer. Independent cohort studies are recommended to confirm these findings and further explore their clinical utility.

Introduction: Evidence indicates that the FAM72 gene family may play oncogenic roles in multiple cancers. This study aimed to investigate alterations in the expression of the FAM72B gene (a member of the FAM72 gene family) across various common cancers (pan-cancer), with particular emphasis on breast cancer. Additionally, the study examined the correlation between FAM72B expression levels and patient survival. Methods: Differential expression of FAM72B in various cancers was investigated based on the Cancer Genome Atlas (TCGA) data. The association of FAM72B level with patient mortality was examined using TCGA clinical data, with univariate Cox regression and Kaplan-Meier curves. Using the co-expression network, potential pathways related to FAM72B were identified. Next, the expression level of FAM72B in breast cancer (BC) samples and its association with genes related to cell proliferation were examined using RT-qPCR. Results: A significant increase in FAM72B gene expression level was observed in bladder, breast, colorectal, head and neck, endometrial, liver, various lung, kidney, and stomach cancers. Our results showed that increased FAM72B gene expression was significantly associated with poor prognosis in bladder, breast, colorectal, kidney, liver, lung, and endometrial cancers. The co-expression network revealed that FAM72B expression was correlated with genes involved in cell proliferation, including CDK1 and CCNB1 . RT-qPCR results also showed that FAM72B expression was higher in BC samples than in adjacent normal tissue. Additionally, the expression levels of CDK1 and CCNB1 were significantly correlated with FAM72B expression in the samples evaluated. Conclusion: This study found that the FAM72B gene was overexpressed in prevalent cancers and could be associated with poor patient prognosis and pathways related to cell proliferation. Our findings suggest that the FAM72B level may have oncogenic potential across multiple cancer types and could be considered a prognostic biomarker.

High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and aggressive subtype among ovarian cancers and is associated with poor prognosis. The molecular mechanism of HGSOC development and metastasis is complex and associated with genomic instability due to abnormal DNA repair systems. This leads to the loss of tumor suppressors and amplification of oncogenes that are accompanied by epigenetic alterations. Despite its name and complexity, there is debate about its origin; however, recent findings on genetic and epigenetic features in animal models and human samples suggest that fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) are the main origin sites of HGSOC development. Since OSE-derived tumors are associated with chemoresistance and poor survival rates, understanding HGSOC origin is clinically valuable for selecting appropriate treatment. This review focuses on the early genetic and epigenetic changes that characterize tumors originating from FTE versus OSE, highlighting how these differences may influence clinical behavior and treatment response. Uncovering the early molecular mechanisms that drive the distinct origins of HGSOC is essential for a deeper understanding of how this cancer develops. These insights could pave the way for the development of precise, biomarker-based strategies for early detection and more effective treatment. In line with this goal, the final section of our review highlights emerging non-invasive screening methods such as mutation and epigenetic profiling of circulating tumor DNA (ctDNA), along with transcriptomic analysis of microRNAs in body fluids. These emerging approaches show strong potential as biomarkers for early diagnosis and for predicting patients’ therapy response. Graphical abstract Studies using engineered animal models, organoids, and human patient samples suggest that high-grade serous ovarian cancer (HGSOC) originates from both the fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE), each with distinct genetic and epigenetic mechanisms and clinical outcomes. Identifying the early molecular changes associated with each origin may facilitate the discovery of diagnostic and prognostic biomarkers for early-stage HGSOC screening.

Objective: Breast Cancer (BCa) remains the leading cause of cancer-related mortality among women, underscoring the need for developing more effective novel biomarkers. This study investigated the role of Growth Arrest-Specific 2 (GAS2) and its co-expressed genes in breast cancer. Methods: RNA-Seq data from 60 matched normal and malignant breast tissue samples (GSE183947) were analyzed. Expression values were normalized using FPKM, and GAS2 co-expression networks were constructed with SUM Lasso and linear regression. Gene-gene interaction networks were examined using Gephi software. Results: GAS2 expression was significantly reduced in tumors compared with normal tissues (p < 0.01). Distinct sets of GAS2-associated genes were identified in cancer versus normal tissues, with tumor-associated partners (TAS2R14, PHF21B, CNTN5, UGT2B15) linked to drug metabolism and signaling, and normal-associated partners (DCC, STAT5A, ZCRB1) linked to transcriptional and cytoskeletal regulation. Network analysis revealed substantial differences in gene expression patterns between tumor and normal tissues, indicating GAS2’s involvement in cancer-specific signaling pathways. Conclusion: GAS2 displays context-dependent gene interactions and reduced expression in BCa, suggesting potential relevance to tumor biology. While these findings support its value as a candidate biomarker, experimental validation is required before translational applications can be established.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths globally. Enhancer of zeste homolog 2 (EZH2), a methyl-transferase and master transcriptional regulator frequently overexpresses in a variety of malignancies. Long non-coding RNAs (lncRNAs) play a significant role in regulating gene expression and are intricately involved in the EZH2 oncogenic regulatory network. We aimed in this study to investigate the expression of EZH2-associated lncRNAs and their probable regulatory role in GC progression. RNA-seq and miRNA-seq data from 375 tumor and 32 normal samples were retrieved from the TCGA database. Differential expression and correlation analyses were performed to identify EZH2-associated lncRNAs. A competing endogenous RNA (ceRNA) network comprising lncRNAs, miRNAs, and mRNAs was constructed and visualized. Functional genomics analysis including EZH2 knockdown and induced overexpression experiments were carried out in AGS and MKN-45 GC cell lines to validate the expression of selected lncRNAs using RT-qPCR. EZH2-correlated analysis revealed 16 upregulated and 8 downregulated lncRNAs with significant associations. EZH2 expression modulation studies confirmed that expression levels of lncRNAs including PVT1, MNX1-AS1, AC103702.2, PCAT7, LINC01235, LINC02086, MIR99AHG, and MAGI2-AS3 were regulated by EZH2 in GC cells. EZH2 modulates the expression of several key lncRNAs associated with gastric cancer progression, suggesting that the EZH2/lncRNA axis could serve as a potential therapeutic target. Targeting this axis may open new avenues for influencing critical molecular pathways involved in GC development. Graphical Abstract

Background: Breast and ovarian cancers are prevalent among women, prompting researchers to focus on developing new pharmaceutical agents and innovative drug delivery systems aimed at enhancing treatment efficacy while minimizing side effects. Steviol glycosides offer a promising approach to cancer treatment due to their broad anticancer activity, low toxicity, selective targeting of cancer cells, and potential to enhance chemotherapy efficacy. Objectives: This study explores the potential of steviol glycoside, a natural compound derived from the Stevia rebaudiana plant, as an anticancer agent targeting breast (MCF-7) and ovarian (A2780) cancer cell lines. Methods: MCF-7 and A2780 cells were cultured under standard conditions and treated with varying concentrations of steviol glycoside (0, 10, 20, 30, 40, and 50 µM) over different time points (24, 48, and 72 hours). Cell viability was assessed using the MTT assay, and the expression of apoptotic and anti-apoptotic genes was evaluated. Statistical analyses were performed using a t-test, with P-values calculated based on a significance threshold of 0.05. Graphs were generated using GraphPad Prism software. Results: The inhibitory concentration 50% (IC50) values for MCF-7 cells were 30 μM, 24 μM, and 22 μM at 24, 48, and 72 hours, respectively. For A2780 cells, the corresponding IC50 values were 24 μM, 20 μM, and 19 μM at the same time points. The fold change in Bax and Bad gene expression increased with rising concentrations of steviol glycoside. At concentrations above 20 μM, this increase became statistically significant (P < 0.001). Conversely, Bcl-2 gene expression exhibited a statistically significant decrease (P < 0.001) at these concentrations. Conclusions: The findings highlight the therapeutic potential of steviol glycoside in treating breast and ovarian cancers, emphasizing the need for deeper investigation into its molecular pathways to fully understand its mechanisms. Despite its promise, significant challenges exist in translating laboratory results into clinical applications. Key obstacles include establishing appropriate dosing, assessing interactions with other medications, and conducting comprehensive trials to ensure safety and efficacy. Acknowledging these limitations enhances transparency and underscores the necessity for additional research to progress toward human trials.