Molecular biology and breast cancer

Radio genomics is an exciting new area that uses diagnostic imaging to discover genetic features of diseases. In this review, we carefully examined existing literature to evaluate the role of artificial intelligence (AI) and machine learning (ML) on dynamic contrastenhanced MRI (DCE-MRI) data to distinguish molecular subtypes of breast cancer (BC). Implications to noninvasive assessment of molecular subtype include reduction in procedure risks, tailored treatment approaches, ability to examine entire lesion, follow-up of tumour biology in response to treatment and evaluation of treatment resistance and failure secondary to tumour heterogeneity...

Cancer is a broad classification of diseases that can affect any organ or body tissue due to aberrant cellular proliferation for unknown reasons. Many present chemotherapeutic drugs are highly toxic and have little selectivity. Additionally, they lead to the development of medication resistance. Therefore, developing tailored chemotherapeutic drugs with minimal side effects and good selectivity is crucial for cancer treatment. 2-(1 H )-Quinazolinone is one of the vital scaffold and anticancer activity is one of the prominent biological activities of this class...

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy worldwide. >70 % of AR expression in primary and metastatic breast tumors has been observed which suggests that AR may be a new marker and a potential therapeutic target among AR-positive BC patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. Downstream signaling of AR might also affect many clinically important pathways that are emerging as clinical targets in BC...

Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity...

HER2-enriched (HER2+ ) breast cancers express high levels of the growth-promoting HER2 protein. Although these cancers are treated with the HER2-targeted drug, trastuzumab, resistance to treatment is common. Retinoic acid (RA) is an anti-cancer agent that has been successfully used for the treatment of leukemia and holds promise for the treatment of solid cancers, including breast cancer. The HER2 gene is frequently co-amplified with RARA, a key determinant of RA sensitivity in breast cancers. It seems surprising, therefore, that HER2+ breast cancers are refractory to RA treatment...

Tumor tissues often contain high extracellular adenosine, promoting an immunosuppressed environment linked to mesenchymal transition and immune evasion. Here, we show that loss of the epithelial transcription factor, GRHL2, triggers NT5E/CD73 ecto-enzyme expression, augmenting the conversion of AMP to adenosine. GRHL2 binds an intronic NT5E sequence and is negatively correlated with NT5E/CD73 in breast cancer cell lines and patients. Remarkably, the increased adenosine levels triggered by GRHL2 depletion in MCF-7 breast cancer cells do not suppress but mildly increase CD8 T cell recruitment, a response mimicked by a stable adenosine analog but prevented by CD73 inhibition...

Gynecological cancers, encompassing endometrial, ovarian, and cervical cancer, pose significant challenges in clinical practice, often marked by high mortality rates and treatment resistance. Despite advances in standard therapies, including chemoradiation and surgery, tumor recurrence and metastasis remain formidable obstacles. In this context, there is a pressing need to explore novel therapeutic strategies that offer improved efficacy and reduced side effects. Herbal medicine, particularly compounds like resveratrol, has garnered attention for its diverse biological properties, including anticancer effects...

More women die of breast cancer than of any other malignancy. The resistance and toxicity of traditional hormone therapy created an urgent need for potential molecules for treating breast cancer effectively. Novel biphenyl-substituted pyrazole chalcones linked to a pyrrolidine ring were designed by using a hybridization approach. The hybrids were assessed against MCF-7 and MDA-MB-231 cells by NRU assay. Among them, 8k, 8d, 8m, 8h, and 8f showed significantly potent IC50 values: 0.17, 5.48, 8.13, 20.51, and 23...

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines...

BACKGROUND: Endophytic fungi have an abundant sources rich source of rich bioactive molecules with pivotal pharmacological properties. Several studies have found that endophytic fungi-derived bioactive secondary metabolites have antiproliferative, anti-oxidant, and anti-inflammatory properties, but the molecular mechanism by which they induce cell cycle arrest and apoptosis pathways is unknown. This study aimed to determine the molecular mechanism underlying the anticancer property of the endophytic fungi derived active secondary metabolites on human breast cancer cells...

Single-cell technologies offer insights into molecular feature distributions, but comparing them poses challenges. We propose a kernel-testing framework for non-linear cell-wise distribution comparison, analyzing gene expression and epigenomic modifications. Our method allows feature-wise and global transcriptome/epigenome comparisons, revealing cell population heterogeneities. Using a classifier based on embedding variability, we identify transitions in cell states, overcoming limitations of traditional single-cell analysis...

A Schiff-base Ethyl (E)-2-(3-((2-carbamothioylhydrazono)methyl)-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (TZTS) dual functional colorimetric and photoluminescent chemosensor which includes thiazole and thiosemicarbazide has been synthesized to detect arsenic (As3+ ) ions selectively in DMSO: H2 O (7:3, v/v) solvent system. The molecular structure of the probe was characterized via FT-IR, 1 H, and 13 C NMR & HRMS analysis. Interestingly, the probe exhibits a remarkable and specific colorimetric and photoluminescence response to As3+ ions when exposed to various metal cations...

Cancer stem cells (CSCs) are a subpopulation of cancer cells within tumors that exhibit stem-like properties and represent a potentially effective therapeutic target toward long-term remission by means of differentiation induction. By leveraging an artificial intelligence approach solely based on transcriptomics data, this study scored a large library of small molecules based on their predicted ability to induce differentiation in stem-like cells. In particular, a deep neural network model was trained using publicly available single-cell RNA-Seq data obtained from untreated human-induced pluripotent stem cells at various differentiation stages and subsequently utilized to screen drug-induced gene expression profiles from the Library of Integrated Network-based Cellular Signatures (LINCS) database...

Activating mutations in PIK3CA are frequently found in estrogen-receptor-positive (ER+) breast cancer, and the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib with anti-ER inhibitors is approved for therapy. We have previously demonstrated that the PI3K pathway regulates ER activity through phosphorylation of the chromatin modifier KMT2D. Here, we discovered a methylation site on KMT2D, at K1330 directly adjacent to S1331, catalyzed by the lysine methyltransferase SMYD2. SMYD2 loss attenuates alpelisib-induced KMT2D chromatin binding and alpelisib-mediated changes in gene expression, including ER-dependent transcription...

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways...

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function)...

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Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months...

In precision oncology, reliable testing of predictive molecular biomarkers is the prerequisite for optimal patient treatment. Interlaboratory comparisons are a crucial tool to verify diagnostic performance and reproducibility of one's approach. Here, we describe the design and results of the first recurrent, internationally performed PIK3CA Breast Cancer Tissue external quality assessment (EQA), which was organized by German Quality in Pathology (QuIP) GmbH and started in 2021. After the internal pretesting phase performed by the (lead) panel institutes, in both 2021 and 2022, each EQA test set comprised n=10 tissue samples of hormone receptor-positive, human epidermal growth factor receptor 2-negative invasive breast cancer (IBC) that had to be analyzed and reported by the participants...

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes...