Personalized and Precision Medicine Journal

Abstract Breast cancer is responsible for more than 2.3 million newly diagnosed cases each year, according to the statistics. A hormonal imbalance, which is defined by unregulated activity of estrogen and progesterone, is often the cause of this type of cancer. It has become easier to handle patients who have HR+ breast cancer, particularly in women who have both advanced and early-stage disease, as a result of the deployment of estrogen-blocking hormone treatment. The permissiveness of tamoxifen, which was the first selective estrogen receptor modulator (SERM) to be commercialized, made it possible for more hormonal therapies to be developed. The cornerstone of breast cancer treatment is comprised of aromatase inhibitors (AIs), selective estrogen receptor degraders (SERDs), and cyclin-dependent kinase inhibitors (CDK) 4/6. These three types of drugs ultimately lead to improved patient outcomes. On the other hand, the inherent or acquired resistance of cancers to hormone therapy continues to be a serious cause for concern. Alterations in the genetic makeup of the tumor, as well as the activation of alternate pathways, make this situation even worse. The increasing development of molecular biology, precision medicine, and targeted therapies, on the other hand, is pointing to a new strategy for dealing with these problems. The purpose of this study is to investigate prospective treatment options and to shed light on the significant role that hormone therapy plays in the management of HR-positive breast cancer.

Abstract Background: Breast cancer is the most common malignancy among women in Iran, characterized by a relatively early age of onset and a rising incidence rate. The single-nucleotide polymorphisms rs2981582 and rs1219648, located in intron 2 of the FGFR2 gene, have been linked to breast cancer susceptibility in genome-wide association studies (GWAS). Nevertheless, their significance in the Iranian population has not been extensively investigated.
This study investigates the association of FGFR2 polymorphisms (rs2981582 and rs1219648) with breast cancer risk in Iranian women, alongside haplotype interactions and gene expression profiling.
Methods: A case-control study was conducted with 160 participants (80 cases and 80 age-matched controls). FGFR2 SNPs were genotyped with PCR-RFLP. Chi-square tests were used to analyze associations of haplotypes. FGFR2 expression was evaluated in breast cancer subtypes using GEO (GDS2635, GDS3853) and Expression Atlas datasets. Statistical analyses were carried out using SPSS version 22.0 (IBM Corp., Armonk, NY, USA), with statistical significance defined as P<0.05. Hardy–Weinberg equilibrium (HWE) was verified for both SNPs in the control group (P>0.05).
Results: The TT genotype of rs2981582 was significantly associated with increased breast cancer risk (P=0.00; OR=3.566). No independent association was found for rs1219648 (P>0.05). Haplotypes AC and AT were significantly associated with elevated risk (P=0.004 and P=0.001, respectively). FGFR2 expression was upregulated in lobular carcinoma and downregulated in ductal carcinoma compared to healthy controls (P<0.05).
Conclusion: The rs2981582 TT genotype and specific haplotypes (AC, AT) are associated with increased breast cancer risk in Iranian women, supporting FGFR2 as a potential biomarker for early detection and personalized risk assessment in this population.

Abstract Background and Objective: Gene therapy can be employed to treat several disorders, including cancer. Globally, women are more frequently diagnosed with breast cancer than any other cancer type, underscoring the necessity for innovative strategies. Algorithms driven by artificial intelligence can enhance the gene therapy process for breast cancer by analyzing vast data sets, identifying intricate patterns, and classifying those patterns. This project aims to perform a literature evaluation focusing on the therapeutic uses of artificial intelligence in gene therapy for breast cancer.

Materials and Methods: For the aim of this study, data was gathered by reading previously published articles and searching the PubMed database for phrases that were relevant to the question being investigated.
Findings: The AI-driven algorithm analyzes complex molecular pathways in the human body, replicates the knowledge of scientists and physicians in clinical research, and simulates biological processes related to gene regulation, thereby improving the effectiveness of gene vectors, managing gene and drug delivery parameters, and modeling cellular behavior. This method diminishes medical errors and promotes early disease identification and drug efficacy forecasting, thereby providing patients with optimal results from advanced treatments like gene therapy with minimal side effects.
Conclusion: Over the period of the past decade, a multitude of efforts have been made to deploy various gene therapy procedures for breast cancer patients, to achieve the highest possible level of efficacy while minimizing the risk of adverse consequences. As a result, artificial intelligence is considered to be a powerful tool for improving early diagnosis and efficient gene therapy for breast cancer.

Abstract Cancer remains one of humanity's leading causes of both illness and death globally. In women worldwide, breast cancer remains the most widespread malignant condition. The new possibilities for direct treatment offered by the advances made thereby were the subject of the recent study undertaken as it sought to unravel tumorigenesis through genetics and molecular appreciation of cancer. Specifically, this research centers on devising and testing immunotoxins as anti-bacterial toxin-based constructs to treat breast cancer. These immunotoxins can kill cancer cells selectively while leaving normal tissues unharmed as they bind only to cancer cell antigens by using both the specificity of antibodies and bacterial toxins' cytotoxicity power. We assessed immunotoxins' binding affinities to their respective antigens based on computational dockings like HADDOCK explaining encouraging results characterized by good docking scores accompanied by low RMSDs—also, dual targeting approaches combined with structure-based. By developing humanized antibodies and novel targeting moieties, challenges such as immunogenicity and non-specific toxicity have been tackled. Our findings suggest that optimized immunotoxins
have great potential to enhance therapeutic window as well as efficacy in cancer treatments

Abstract Free radicals are naturally produced in the body and are inhibited by the body’s antioxidants. The excessive production of free radicals and the inability of the body to remove them lead to oxidative stress in the body, which can lead to many diseases, including cancer. Nanoparticles are compounds that have been given much attention to cancer prevention and treatment, due to their specific biological characteristics and their small size. This study aimed to evaluate the cytotoxic and antioxidant potential of serum oxide nanoparticles synthesized using aqueous extract of Hyssopus officinalis.
To perform the MTT assay, first, the MDA-MB231 cancerous cells were cultured, seeded and then treated for 24, 48 and 72 hours. Subsequently, MTT was performed and finally, absorption at 517 nm was recorded. The antioxidant potential of the CeO-NPs was evaluated by estimating the amount of ABTS and DPPH free radicals inhibiting in different concentrations of nanoparticles.
The results showed that the CeO-NPs were able to inhibit the ABTS and DPPH free radicals with a mean concentration (IC50) of about 62 and 31.2 μg / ml. Also, the CeO-NPs inhibited cancer cells with IC50 of about 400 µg/ml, 48 hours after exposure. According to the antioxidant results obtained from this paper, it is suggested that by performing further experiments, this nanoparticle can be used as an antioxidant supplement.

Abstract Immunotoxins have been used for cancer treatment. The immunotoxin binds to the surface antigen on the cancer cell, enters inside the cell by endocytosis1, and destroys the cancer cell. In addition, the components of this type of drug and assembly based on peptide bonds2, and the creation of recombinant protein construction were among the requirements investigated in this study. In this bioinformatics research, membrane antigen structural, and functional properties on the surface of breast cancer cells were investigated and evaluated to target cancer cells. An EGFR3 antigen with a shorter amino acid length for positive binding and INS4, which has 110 amino acids, binding +, and a binding score of 0.99, was selected as the most efficient ligand using the AAASGG 3 (GGGGS) linker5, resulting in a six-recombinant structure. Hence, the targeted treatment of cancer through immunotoxin with the confirmation of the patent sequence led to the creation of a recombinant structure, which was analyzed with bioinformatics software. To ensure accurate results in the laboratory, we utilized Escherichia coli strain DH5 as a host during the cloning phase for plasmid DNA replication. This enabled a more precise and reliable replication process, thereby confirming the validity of our computational modeling, and the results of this research led to the modeling and simulation of the engineering structure of Cetuximab ZZpe38 immunotoxin. For future research, gene expression in mammalian cells will be the focus.

Abstract Background
Cancer associated thrombotic microangiopathy (CA-TMA) is a rare diagnosis that while confronting a patient with evidence of microangiopathic hemolytic anemia and thrombocytopenia with normal ADAMTS13 enzyme activity, should be considered. Here we present two cases of cancer associated TMA; breast cancer and gastric cancer.
Case presentation
Case 1 was a 40-year-old man presented with abdominal pain, icterus and weight loss and laboratory tests revealed microangiopathic hemolytic anemia. He received 6 sessions of plasma exchange under diagnosis of thrombotic thrombocytopenic purpura. Bone marrow biopsy and immunohistochemistry revealed clusters of non-hematopoietic cells suggestive of gastrointestinal adenocarcinoma. Case 2 was a 51-year-old woman whose clinical history and laboratory tests were similar to case 1 except for a breast mass along with axillary lymphadenopathy. Bone marrow examination revealed clusters of non-hematopoietic cells and core needle biopsy revealed invasive lobular carcinoma.
Both patients were unresponsive to plasma exchange and case 1 unfortunately shortly died after diagnosis but case 2 is alive and survived after receiving chemotherapy. 
Conclusion
Cancer associated TMA can rarely be seen as the first manifestation of a malignancy and causes a diagnostic dilemma for clinicians.The prognosis of CA-TMA is generally poor and initiatingchemotherapy is the only reliable treatment option.

Abstract The pathophysiology and molecular pathways of breast cancer (BC) are still unclear, but it appears that BC is caused by the interaction between genetic susceptibility and environmental factors. Epidemiology studies have shown the increase risk of BC through polycyclic aromatic hydrocarbons (PAH) exposure. Environmental carcinogens induce disease pathways by altering the expression of specific genes that may be a consequence of epigenetic modifications. In order to understand the effects of PAHs in the BC risk, the epigenetic pathway may consider as an important key and likely play a role in BC initiation. Novel epigenetic  biomarkers and treatments hold promise  in the approch of personalized medicine. Here, we focus to review the epigenetic factors in relation to polycyclic aromatic hydrocarbons exposure that may influence BC risk.

Abstract Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development. Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. Understanding the biological intricacies of the EMT may provide important insights that lead to the development of therapeutic targets in pre-invasive and invasive breast cancer, and could be used as biomarkers for identifying tumor subsets with greater chances of recurrence, metastasis, and therapeutic resistance leading to death. The purpose of this article is to investigate the association between EMT and breast cancer.

Abstract Personal medicine is based on purposeful treatment that, unlike traditional therapies, considers a person's genetic structure and medical history before establishing a treatment regimen. This science has made possible the improvement of "pharmacogenomic" knowledge, which identifies individuals who respond to a particular treatment based on their genotype information. The findings of the Cancer Genome Atlas Network show that each molecular endorsement of each BCis unique. Also, different responses to a given medication regimen have been reported among a similar group of breast cancer. Thus, personal medicine plays a role in the care of patients with breast cancer, in which a person's characteristics, including genetic characteristics, guide clinical decisions and are effective in choosing the right treatment for the patient at the right time.

Abstract One of the key molecular mechanisms contributing to the metastatic progression is epithelial to mesenchymal transition (EMT), which drives invasion and migration of various cancer including breast cancer.During tumorigenesis, changes in EMT regulatory pathways lead to a loss of cellular adhesions, changes in the polarization of the cell and cytoskeleton, detachment, migration, intra-vasation, and survival in the vascular system; extravasation, and finally, metastasis.EMT is largely mediated by a core set of EMT-activating transcription factors. The master regulators of the EMT include many pathways, however the primary mediators of the EMT include signaling through TGF-, Notch and Wnt.  The role of EMT in breast cancer has  been demonstrated via numerous in vitro studies in  normal and malignant mammary epithelial cells and via in vivo studies using mouse models of breast cancers. Studying the regulatory pathways of the EMT process can be used as a tool for cancer monitoring ,treatment and possible direct targets for new-combination anticancer personalized medicine.

Abstract Hesperidin is a flavanone present in citrus fruits, such as oranges and lemons. It exerts non-toxic activities in normal cells; however, it has been reported to suppress cell proliferation in several cancer types. Moreover, it was shown that dietary hesperidin acts as an anti-carcinogenic agent for some tumors. In the present study, we investigated the effect of hesperidin on breast cancer cell line MCF7 and also its effects on the expression of apoptosis-related genes in this cell line.
MCF7 cells were divided into 4 groups, including 3 study groups and 1 control group. Each study group was treated with 50, 75, or 100 μg/mL hesperidin, while the control group was left untreated. The samples underwent real-time PCR using the primers specific for BCL-2 and BAX, as the study genes, while GAPDH was used as the control.
According to our findings, hesperidin caused a significant decrease in BCL-2 mRNA levels at all the doses used in the study groups compared to the control group (p < 0.002). The observed decrease was dose-dependent. Also, hesperidin induced a significant overexpression of BAX when used in doses of 75 and 100 µg/mL in comparison to the control group.
The present study proved the significant apoptosis-inducing effect of hesperidin on the breast cancer cell line MCF7.

Abstract Breast cancer is the most common cancer in women, and its frequency is rising in countries with low and middle incomes. The influence of diet on mammary carcinogenesis has been clearly demonstrated in animal models. Inadequate folate intake has been associated with several cancers, and low levels of serum folate, vitamin B6, and vitamin B12 have been associated with increased breast cancer risk. The levels of folic acid, B6, and B12 in the plasma of 85 people with breast cancer were measured and compared with healthy people. A significant inverse trend was observed between folate intake (p-value=0.004) and vitamin B6 intake (p-value=0.0001) and breast cancer risk. Data from this study suggests that B vitamins, including folate, vitamin B-6, and vitamin B-12, may confer little or no reduction in overall risk of developing breast cancer.

Abstract Vitamin C plays is a cofactor for enzymes involved in many processes and has effects that are important for cancer transformation, such as antioxidant defense, transcription, and epigenetic regulation of gene expression.Angiogenesis is a normal process required for normal tissue repair and growth. Pathological angiogenesis is characterized by the persistent proliferation of endothelial cells and formation of blood vessels.The current study evaluated the effect of ascorbic acid on angiogenesis by investigating the expression of genes related to angiogenesis after treatment with different doses of ascorbic acid. By changing the concentration and administration time of ascorbic acid, a positive effect on the growth and metastasis of cancer cells in the group injected with ascorbic acid prior to having cancer cells injected into the abdominal cavity .



 

Abstract The majority of ncRNAs are known as long non-coding RNAs (lncRNAs) whose length exceeds 200 nucleotides. H19, a lncRNA, is the transcription product of the H19 gene, an oncogene in breast cancer, and is highly expressed in cancer tissues compared with normal tissues. The expression level of H19 is associated with the oncogenesis, proliferation, invasion, metastasis, and drug resistance of breast cancer. H19 expression levels were detected in breast cancer plasma using qRT-Real-Time PCR assay in 50 breast cancer samples and 50 healthy control samples. The results showed that the expression of this gene in both the tissue and the plasma of patients increased compared to that of healthy individuals.

Abstract Because of their small size, unique physics, and chemical properties, metal nanoparticles can easily cross obstacles and reach their target cells, which makes them an ideal choice for therapeutic purposes in various cancers. In this study, the effects of iron oxide nanoparticles on MDA-MB-231 breast cancer cell line were examined, and biomarkers related to oxidative stress were evaluated. Fe2O3 nanoparticles were suspended in a cell culture medium and diluted to appropriate concentrations (0, 10, 30, 60, and 120 μg/ml) for 24 and 48 h. GSH, superoxide dismutase, catalase, and ROS generation were evaluated. The results showed that iron oxide nanoparticles induced intracellular ROS generation in a dose- and time-dependent manner. The results further showed that iron oxide nanoparticles increased ROS and activated oxidative stress in cells.

Abstract According to the World Health Organization, one in eight to ten women will develop breast cancer. Therefore, the development of new blood / serum markers is important as an alternative to traditional diagnosis methods. Early detection of breast cancer plays an important role in choosing the right treatment approach and treating the patient. In this study, the expression of miRNA21 gene in the plasma sample of people with breast cancer compared to healthy people was evaluated. The results of qPCR showed that the expression levels of miRNA-21 in the plasma samples of breast cancer patients were significantly increased compared to those of the healthy controls. These results suggest that Mir 21 could be a very good blood biomarker for the early detection of breast cancer.