Mechanisms of reduced efficacy of HER2-targeted therapy in HER2-low breast cancer by long-term nicotine exposure in patient-derived xenograft mouse tumor models.

The effects of long-term nicotine exposure on the treatment of HER2-positive breast cancer have only been studied epidemiologically, leaving the molecular mechanisms unclear. Therefore, it's challenging for clinicians to devise effective treatments based on this correlation. Our investigation explores the effects of prolonged nicotine exposure on the interaction between α9-nAChR and HER2 in HER2-positive breast cancer cells, highlighting its impact on anti-HER2 drug therapy efficacy.

Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.

Background: Up to 23% of breast cancer patients recurred within a decade after trastuzumab treatment. Conversely, one trial found that patients with low HER2 expression and metastatic breast cancer had a positive response to trastuzumab-deruxtecan (T-Dxd). This indicates that relying solely on HER2 as a single diagnostic marker to predict the efficacy of anti-HER2 drugs is insufficient.

Fibroblast growth factor receptor four inhibitor FGF401 improves the efficacy of trastuzumab in FGFR4-overexpressing breast cancer cells.

Breast cancer is the most common cancer among women. Among them, human epidermal growth factor receptor-positive (HER2+) breast cancer is more malignant. Fortunately, many anti-HER2 drugs are currently used in clinical treatments to increase patient survival.

Investigation of the α9-nicotinic receptor single nucleotide polymorphisms induced oncogenic properties and molecular mechanisms in breast cancer.

α9-nAChR, a subtype of nicotinic acetylcholine receptor, is significantly overexpressed in female breast cancer tumor tissues compared to normal tissues. Previous studies have proposed that specific single nucleotide polymorphisms (SNPs) in the CHRNA9 (α9-nAChR) gene are associated with an increased risk of breast cancer in interaction with smoking. The study conducted a breast cancer risk assessment of the α9-nAChR SNP rs10009228 (NM_017581.

and Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles.

RNA therapeutics has advanced into the third milestone in pharmaceutical drug development, following chemical and protein therapeutics. RNA itself can serve as therapeutics, carriers, regulators, or substrates in drug development. Due to RNA's motile, dynamic, and deformable properties, RNA nanoparticles have demonstrated spontaneous targeting and accumulation in cancer vasculature and fast excretion through the kidney glomerulus to urine to prevent possible interactions with healthy organs.

Targeted Delivery of Potent Chemical Drugs and RNAi to Drug-Resistant Breast Cancer Using RNA-Nanotechnology and RNA-Ligand Displaying Extracellular vesicles.

This review describes a new technology to treat breast-cancer-drug-resistance by targeting the ABC as the multi-homo-subunit ATPase, enlightening by the Christmas-lighting budge with serial circuit and the asymmetrical homo-hexamer of the phi29 DNA packaging motor with sequential revolving mechanism. Chemotherapeutics has been widely used in breast cancer treatments, but drug resistance has raised a serious concern. RNA therapeutics has emerged as the third milestone in pharmaceutical drug development.

StAR-related lipid transfer domain protein 3 (STARD3) regulates HER2 and promotes HER2-positive breast cancer progression through interaction with HSP90 and SRC signaling.

Although various HER2-targeted therapies have been approved clinically, drug resistance remains a considerable challenge. Studies have found that the cause of drug resistance is related to the expression of genes co-amplified with HER2 in breast cancer cells. Our study found that STARD3 was highly expressed in tumor tissues (n = 130, P < 0.

Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein.

This study demonstrated for the first time that curcumin effectively inhibits the growth of triple-negative breast cancer (TNBC) tumors by inhibiting the expression of salt-induced kinase-3 (SIK3) protein in patient-derived xenografted tumor mice (TNBC-PDX). For TNBC patients, chemotherapy is the only option for postoperative adjuvant treatment. In this study, we detected the SIK3 mRNA expression in paired-breast cancer tissues by qPCR analysis.

Type-3 Hyaluronan Synthase Attenuates Tumor Cells Invasion in Human Mammary Parenchymal Tissues.

The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth.

The α9 Nicotinic Acetylcholine Receptor Mediates Nicotine-Induced PD-L1 Expression and Regulates Melanoma Cell Proliferation and Migration.

Cigarette smoking is associated with an increased risk of melanoma metastasis. Smokers show higher PD-L1 expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Here, we investigate whether nicotine, a primary constituent of tobacco, induces PD-L1 expression and promotes melanoma cell proliferation and migration, which is mediated by the α9 nicotinic acetylcholine receptor (α9-nAChR).

Study of the antitumor mechanisms of apiole derivatives (AP-02) from Petroselinum crispum through induction of G0/G1 phase cell cycle arrest in human COLO 205 cancer cells.

Background: Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells.

Methods: Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with apiole and its derivatives in a dose-dependent manner.

Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3-induced mitophagy.

Neuroblastoma is the second most common pediatric malignancy and has a high rate of spontaneous remission. Uncovering the mechanisms underlying neuroblastoma cell differentiation is critical for therapeutic purposes. A neuroblastoma cell line (N2a) treated with either serum withdrawal (<2.

Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation.

It is well-known that human epidermal growth factor receptor 2 (HER2) is critical for breast cancer (BC) development and progression. Several studies have revealed the role of the ubiquitin/proteasome system (UPS) in cancer. In this study, we investigated the expression level of Proteasome 26S subunit, non-ATPase 3 (PSMD3) in BC using BC cell lines, human BC tissue samples, Oncomine, and TCGA databases and studied the PSMD3-HER2 protein interaction.

Small G protein signalling modulator 2 (SGSM2) is involved in oestrogen receptor-positive breast cancer metastasis through enhancement of migratory cell adhesion via interaction with E-cadherin.

The function of small G protein signalling modulators (SGSM1/2/3) in cancer remains unknown. Our findings demonstrated that SGSM2 is a plasma membrane protein that strongly interacted with E-cadherin/β-catenin. SGSM2 downregulation enhanced the phosphorylation of focal adhesion kinase (FAK; Y576/577), decreased the expression of epithelial markers such as E-cadherin, β-catenin, and Paxillin, and increased the expression of Snail and Twist-1, which reduced cell adhesion and promoted cancer cell migration.

Long-term exposure to extremely low-dose of nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induce non-malignant breast epithelial cell transformation through activation of the a9-nicotinic acetylcholine receptor-mediated signaling pathway.

Breast cancer (BC) is the most common cancer affecting women worldwide and has been associated with active tobacco smoking. Low levels of nicotine (Nic) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have been detected in cases of second-hand smoke (SHS). However, the correlation between SHS and BC risk remains controversial.

Oestrogen receptor-regulated glutathione S-transferase mu 3 expression attenuates hydrogen peroxide-induced cytotoxicity, which confers tamoxifen resistance on breast cancer cells.

Purpose: Glutathione S-transferase mu 3 (GSTM3) is an enzyme involving in the detoxification of electrophilic compounds by conjugation with glutathione. Higher GSTM3 mRNA levels were reported in patients with ERα-positive breast cancer who received only tamoxifen therapy after surgery. Thus, this study aimed to clarify the oncogenic characteristics of GSTM3 in breast cancer and the mechanism of tamoxifen resistance.

Down-regulation of α-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface.

α-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236).

Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft tumors.

Here we report that 3'-hydroxypterostilbene (HPSB), a natural pterostilbene analogue, was more potent than pterostilbene against the growth of human cancer cells (COLO 205, HCT-116, and HT-29) with measured IC50 values of 9.0, 40.2, and 70.

Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells.

Background: Large epidemiological cohort studies in the United States have indicated that active and passive smoking are associated with increased breast cancer risk. However, there was no direct evidence of an effect of tobacco carcinogens on the cellular molecules involved in breast tumorigenesis.

Methods: Reverse transcription-polymerase chain reaction was used to determine the expression of all of the nicotinic acetylcholine receptor (nAChR) subunits in 50 human breast cancer samples and to determine the expression of the alpha9-nAChR subunit in 276 surgical and laser capture microdissected breast tumor vs normal tissue pairs.

Increased expression of enolase alpha in human breast cancer confers tamoxifen resistance in human breast cancer cells.

Enolase-alpha (ENO-1) is a key glycolytic enzyme that has been used as a diagnostic marker to identify human lung cancers. To investigate the role of ENO-1 in breast cancer diagnosis and therapy, the mRNA levels of ENO-1 in 244 tumor and normal paired tissue samples and 20 laser capture-microdissected cell clusters were examined by quantitative real-time PCR analysis. Increased ENO-1 mRNA expression was preferentially detected in estrogen receptor-positive (ER+) tumors (tumor/normal ratio >90-fold) when compared to ER-negative (tumor/normal ratio >20-fold) tumor tissues.